Borrelia Burgdorferi (Lyme Disease) and Hypercoagulation ( nadkrzepliwosc ) test na : Liczba płytek krwi
Nadkrzepliwość lub trombofilia - można zdefiniować jako zmniejszony kapilarny przepływ krwi i skłonność do koagulacji lub skrzepu. Około 900 pacjentow z borelioza tak ma. 90 procent ma nadkrzepliwośc.
-----------------------------
Dr Cheney twierdzi, że w nadkrzepliwości, patogeny i / lub toksyny aktywują układ odpornościowy do odkładania fibryny w naczyniach krwionośnych.
Powłoki ściany fibryny , blokują tlen i substancje odżywcze,ktore nie docierają do okolicznych tkanek. Naukowcy odkryli, że 80% pacjentów z chorobą autoimmunologiczną maja taka sytuacje.
----------------------------
Bromelaina ( extranase )Bromelain i Turmeric lub heparyna - lekiem na nadkrzepliwosc ? czesc lekarzy Ilads zaleca.
Boluoke i Rechtsregulat (acidic ph)- Dr. Klinghardt
Serrapeptase - nutramedix- dr.Cowden
-------------------------------------------------------------------
David Berg jest ekspertem z AZ Coagulation Services in Phoenix :
nadkrzepliwośc
Ocenił skuteczność różnych środków do leczenia nadkrzepliwości :
50% - Bromelain 50% - bromelaina
60% - Wobenzym 60% - Wobenzym
70% - Serrapeptase 70% - Serrapeptase
80% - Nattokinase 80% - Nattokinase
95% - Lumbrokinase 95% - Lumbrokinase
Czosnek, witamina E, oleje rybne i K2 mogą być pomocne przy regulacji krzepnięcia.
Awokado jest najlepszym źródłem witaminy K.
Heparyna jest lekiem, który okazał się pomocny przy leczeniu nadkrzepliwości
http://www.betterhealthguy.com/klinghardt-conference-lyme-and-other-chronic-infections
Dr C: Hypercoagulation, or thrombophilia, may be defined as reduced capillary blood flow or a greater tendency than normal for blood to coagulate, or clot. Of approximately 900 borreliosis patients that I have tested, 90 percent have hypercoagulation. Comparatively, only five percent of the general healthy population has hypercoagulation.
Treatment for hypercoagulation caused by infections is heparin, which is a blood thinner. Typically, heparin is given subcutaneously (under the skin) by injection twice a day in low doses for not more than nine months. It can also be compounded into a troche that dissolves in the mouth, but that is usually more expensive and is often less effective than injections. Symptoms that improve with heparin are pain, fatigue, cognitive problems and neurological problems. About 80 percent of borreliosis patients feel better with heparin, and it has been a safe treatment so far. One patient did develop bleeding from the rectum, but then a colonoscopy revealed a colon cancer that had not yet spread to the local lymph nodes. In other words, the heparin unmasked a hidden malignancy, so in this case the side effect was a blessing.
Heparin is not only a blood thinner, it is also anti-inflammatory, antiviral, antibacterial, and may even be anti-cancer (unproven). Therapy with heparin usually lowers the level of the coagulation components fibrinogen, fibrin, thrombin/antithrombin complexes, fragment 1+2 and Factor II activity. This is desirable, because elevated levels of these coagulation components can cause decreased capillary blood flow, if they are high enough. Capillaries are microscopic blood vessels that are about eight microns wide. A normal red blood cell, which travels through the capillaries, is about seven microns wide. When elevation of coagulation components occur, they could conceivably attach to the inside surface (endothelial surface) of capillaries, thereby narrowing them. For example, fibrinogen attached to the inside surface could make it harder for a seven-micron-wide red blood cell to squeeze through the narrowed capillary. Reduced blood flow in capillaries would in turn reduce oxygen and nutrients, and reduce removal of toxins from tissues. It stands to reason that if heparin could improve blood flow, antibiotics and hormones would be more effective because they could pass through capillaries easier.
Life is in the blood. Less blood flow means less “life,” and possibly more symptoms and diseases -- perhaps even death. Hypercoagulation is associated with other chronic diseases, not just borreliosis. It is my opinion that how hypercoagulation is treated will become a paradigm shift in medicine, once further research has been accomplished.
Hemex Laboratories in Phoenix, AZ has discovered that a number of infections, including mycoplasmas, and Borrelia Burgdorferi can trigger the blood clotting system to become active, preventing oxygen and antibiotics from reaching and destroying the pathogen. This is called hypercoagulation. The Hemex Lab ISAC panel can be run to determine if this is a problem. If this test is positive, appropriate blood thinning agents may be prescribed (Heparin is the preferred choice).
There are a number of problems that must be addressed in patients. For instance, some individuals have a coagulation defect that is set off by the chronic infection Borrelia Burgdorferi (Lyme Disease). This results in the laying down of a fibrin coating on the lumen of the vessel causing impaired oxygen and nutrient transfer. This can result in fatigue, muscle aches and "brain fog". If suspected, diagnosis requires specialized testing (presently only available at Hemex Laboratories in Phoenix) . If not treated, not only are the cells starved for oxygen and nutrients, but it is very difficult to eradicate any infection because they will "hide" in the fibrin coating. If the Coagulation defect is not addressed the defect will limit the antibiotics from reaching and destroying the pathogen
Hypercoagulation leads to "clogging" of our mucous membranes with extra Fibrin and doesn't allow for proper entry into cells of nutrients or egress from cells of waste products. Eventually this causes our interstitial fluids (Terrain) to be filled with toxic waste (Dr. Reckeweg's Homotoxins) and our cells to be deprived of proper nutrients. This leads to all forms of chronic degenerative diseases such as atherosclerosis, Fibromyalgia, arthritis, cirrhosis, emphysema, chronic fatigue and the 100 or so other chronic degenerative diseases.
Dr K: Studies have found that approximately 80% of patients have this low level activation of the clotting system. This low level activation does not produce a blood clot, but rather an intermediate substance called a soluble fibrin monomer (SFM). This coats the inside of the blood vessel and limits oxygen and nutrient flow into the cells. The SFM coating not only limits the oxygen and nutrient flow, but it also provides a place for the spirochete to "hide" and escape destruction by the immune system/antibiotic. Thus, it can be very difficult for patients to rid the body of these infection without treating the Fibrogen Defect. Diagnosis is made by the use of a specialized test called an ISAC (Immune System Activation of Clotting) panel, which measures platelet activation, soluble fibrin monomer, fibrinogen, prothrombin fragment 1 +2 and thrombin/antithrombin complexes. Treatment is low dose heparin and substances to break up the fibrin as well as elimination of the initiating agent, whether it is a virus, bacteria, yeast or toxin. Intervention can be from several weeks to a number of months, if treating with antibiotics Heparin should be continued for the duration of antibiotic treatment.
Growth-Inhibitory Effect of Heparin on Babesia Parasites There is some very current information and an actual study showing that heparin may erradicate Babesia all on it's own and the same may hold true for Lyme- Sabine Bork,1 Naoaki Yokoyama,1 Yuzuru Ikehara,2 Sanjay Kumar,1 Chihiro Sugimoto,1 and Ikuo Igarashi: We examined the inhibitory effects of three heparins on the growth of Babesia parasites. The multiplication of Babesia bovis, B. bigemina, B. equi, and B. caballi in in vitro cultures and that of B. microti in vivo were significantly inhibited in the presence of heparins, as determined by light microscopy. Treatment with various concentrations of heparin showed complete clearance of the intracellular parasites. Interestingly, a higher percentage of abnormally multidividing B. bovis parasites was observed in the presence of low concentrations of heparin. Furthermore, fluorescein isothiocyanate-labeled heparin was preferably found on the surfaces of extracellular merozoites, as detected by confocal laser scanning microscopy. These findings indicate that the heparin covers the surfaces of babesial merozoites and inhibits their subsequent invasion of erythrocytes.
----------------------------------------------------------
Interview with David Berg
David Berg is the Director and Cofounder, with Lois Hill Berg, of HEMEX Laboratories. Along with Dr. Harold Harrison and several clinical collaborators, they have developed the idea of the hypercoagulation/ immune system activation of coagulation theory in chronic diseases, a proposed cause of Chronic Fatigue Syndrome and Fibromyalgia, and have proposed an appropriate treatment that reduces many related symptoms. Mr. Berg has a M.S. degree in clinical pathology and laboratory medicine, and has been in practice for 35 years. HEMEX Laboratories offers testing and consultative services relating to the diagnosis, treatment, and monitoring of hematological, clotting and/or bleeding disorders. We first became involved with research in chronic illnesses while we were performing re search regarding hypercoagulability - related infertility in women with one of the local infertility specialists here in Phoenix, AZ. We found that a hypercoagulable state, presumably due to a coagulation protein defect, existed in many women who were infertile and/or who had recurrent spontaneous abortions. Our colleague Dr. Couvaras observed that when he put women on low dose heparin in order to maintain pregnancy, some with CFS/FM-like symptoms, pelvic pain, and migraine-like headaches had amelioration of their symptoms. He asked us ``Why?'' As a result, we performed a retrospective study on 30 of these obstetric patients with chronic illness symptoms, and determined that all had coagulation system activation. As the hypercoagulability was decreased by heparin injections, the chronic illness symptoms diminished. This was the first clue to the connection between coagulation and chronic illnesses. These findings were published as a poster at the 1998 AACFS meeting in Cambridge, MA. We subsequently refined our test panel for low level activation of coagulation to include Prothrombin fragment 1+2 (F1+2), thrombin/antithrombin complexes (T/AT) and Platelet Activation by Flow Cytometry assays. Thus, the ISAC or Immune System Activation of Coagulation panel consisting of fibrinogen (FIB), soluble fibrin monomer (SFM), F1+2, T/AT, and PA by Flow was born. With our partner and Medical Director, Dr. Harold Harrison and several clinical collaborators, we then designed and conducted a prospective, multi-center, blinded, case control, associative study of non-obstetric CFS/FM patients and controls, with centers in New York, Houston, and Phoenix. When the code was broken, identifying patients and controls, we were able to identify most of the CFS/FM patients based on having two or more positive test results out of the five assays in the ISAC panel. It was the first definitive evidence that, indeed, chronic illnesses have a demonstrable basis in the blood coagulation system. This study was published in the international journal Blood Coagulation & Fibrinolysis, 1999, 10:435-438. In another associative cohort study published in Blood Coagulation & Fibrinolysis, 2000, 11:673-678, we determined that Gulf War illness has similar findings of low level activation of coagulation. In November, 1999, Dr. Joe Brewer (an Infectious Disease specialist in Kansas City) and I developed a model of pathogen activation of the immune and coagulation systems. The model proposes that the end result of such pathogenmediated activation is increased blood viscosity due to 1) an underlying coagulation regulatory protein defect, and 2) activation of the coagulation system by the pathogen. As the blood viscosity increases, the diminished blood flow creates hypoxia (lack of oxygen) and nutrient deprivation within various areas of the body. This is like trying to start your car in Wisconsin in the winter with 60- weight engine oil. This model explains the multi-organ symptomatology and also explains why the low dose heparin therapy is effective by increasing blood flow as the blood viscosity decreases. Thus, patients gain relief from their symptoms with this therapy. The model states that coagulation activation generates thrombin, which converts fibrinogen to soluble fibrin monomer (SFM). Soluble fibrin becomes deposited in the micro-circulation (capillaries) as fibrin or fibrinoid-like deposition, blocking oxygen and nutrients transfer to parenchymal tissues. Many pathogens activate the immune system. These include viruses (such as EBV, CMV, HHV6 & others), bacteria (mycoplasma, chlamydia, borrelia, etc), fungi (such as candida), etc. These pathogens are anaerobes, i.e., they live and reproduce in an oxygen deprived cellular matrix or environment. That's why fibrin deposition becomes important to the survival of the pathogens because it produces decreased oxygen in cells and tissues. One of the biggest challenges to a clinician is to figure out what pathogens are present in the patient, and therefore the most appropriate therapies against these pathogens. The average CFS/FM patient may have anywhere from one to seven pathogens that need eradication. Positivity of two or more tests in the ISAC panel occurs in more than 80% of all patients tested. However, the longer a patient has been ill (many years), the less activation is needed by the pathogens for survival, and therefore fewer tests may be positive. Someone who has been ill for 10 years or more may only have one test positive in the panel. The ISAC panel also works very well for monitoring anticoagulant therapy between 4-6 weeks after therapy has started. It indicates whether or not there is enough heparin being given to the patient, the overall patient improvement and the reaction of the body to the pathogens, such as a Herxheimer-like reaction (relapse from infections or reactivation of pathogens). In addition to the pathogens that can activate the immune system, metals (e.g. mercury, lead, aluminum), exogenous toxins, chemicals, allergens, physical trauma, vaccinations, and/or biological warfare agents can also activate the immune system. This may lead to secondary infections, which may also trigger coagulation activation. If the coagulation mechanism does not shut down properly, then there is continued thrombin generation and soluble fibrin formation, resulting in increased blood viscosity and decreased blood flow. When you look for a genetic basis in this model, one can test for seven different regulatory proteins of the coagulation mechanism plus homocysteine in a panel we call the HTRP (Hereditary Thrombosis Risk Panel). In July 2001, at the International Society of Thrombosis and Hemostasis meeting in Paris, we presented data from a retrospective study of over 400 chronically ill patients, 83% had one or more demonstrable coagulation protein defects. Forty percent of the patients had a thrombophilia defect (decreased protein C, decreased protein S, decreased anti-thrombin, APC resistance/factor V Leiden positivity, or increased prothrombin/prothrombin gene mutation positivity). 39% of the patients have defects in the fibrinolytic system (hypofibrinolysis due to elevated lipoprotein (a) - Lp(a) and/or PAI1-plasminogen activator inhibitor-1. 21% of these patients had a defect in both the thrombophilia and hypofibrinolysis marker groups. This means that not only do they form fibrin easily, but also they are compromised in the ability to clean up the fibrin deposition. Let's put this in plain English. When a pathogen(s) gains a foothold, especially in the endothelial cells in the blood vessels (as well as other cells), the bug(s) can be protected by the coagulation mechanism of fibrin deposition on top of the infected cells. Half of the patients form fibrin very fast, becoming fibrin(oid) deposition. Half of the patients have an inability to clean up the fibrin, and therefore continue to have oxygen and nutrient starvation of tissues for a long time. For example, if the fibrin deposition occurs in a muscle, it says ``ouch,'' and you have a tender point as in Fibromyalgia. If it is in the placenta, the placenta is compromised by fibrin deposition and the baby aborts. As blood viscosity increases and blood flow is reduced throughout the body, the patient becomes hypo-this and hypo-that, such as hypothyroid, hypo-HPAaxis, hypo-estrogen, etc. The use of low dose heparin restores blood flow throughout the body and hormones from the endocrine system tend to normalize. Thus, the blood flow issue becomes one of the most important issues of chronic illnesses. Unfortunately there is no easy test to measure blood flow, only the effects of blood flow. If you consider the movie ``Braveheart'' (1000 AD) and you went to battle and were wounded, you probably would have bled to death unless you clotted fast. By clotting fast, you saved your own life and passed on this new trait to your children. This hypothesis may explain how these coagulation defects were genetically selected during the last 2000 years in Europe. Life expectancy back then was only 30-40 years. With our life expectancy now of 80+ years, these traits are no longer beneficial, but rather deleterious to our health. It was the Spanish, French, British, Germans, Italians, Scandinavians, etc. (Europeans) that colonized the Americas. This explains why most of the chronically ill patients are white people of European decent. Therefore we have a genetic basis in the coagulation system for chronic illnesses that is very straightforward.
The model of reduced blood flow from increased blood viscosity due to activation of coagulation accompanied by a coagulation protein defect gives a scientific basis for a contribution to the pathophysiology of chronic illness. It also gives a measurable or quantifiable, objective aspect to testing the blood of patients with these diseases. It is no longer ``all in your head'', but rather in your ``blood.'' It's not rocket science, but a simple, logical explanation for what's going on in many chronically ill patients.
HEMEX Laboratories provides testing services and consultative interpretations to clinicians and physicians throughout the United States. For more information, technical reprints, and/or patient information, please see their website at www. hemex.com
http://www.springboard4health.com/notebook/health_hypercoagulation_ill.html
--------------------------------------------------------------------------------
Hypercoagulation
Nadkrzepliwość lub trombofilia - można zdefiniować jako zmniejszony kapilarny przepływ krwi i skłonność do koagulacji lub skrzepu. Około 900 pacjentow z borelioza tak ma. 90 procent ma nadkrzepliwośc.
-----------------------------
Dr Cheney twierdzi, że w nadkrzepliwości, patogeny i / lub toksyny aktywują układ odpornościowy do odkładania fibryny w naczyniach krwionośnych.
Powłoki ściany fibryny , blokują tlen i substancje odżywcze,ktore nie docierają do okolicznych tkanek. Naukowcy odkryli, że 80% pacjentów z chorobą autoimmunologiczną maja taka sytuacje.
----------------------------
Bromelaina ( extranase )Bromelain i Turmeric lub heparyna - lekiem na nadkrzepliwosc ? czesc lekarzy Ilads zaleca.
Boluoke i Rechtsregulat (acidic ph)- Dr. Klinghardt
Serrapeptase - nutramedix- dr.Cowden
-------------------------------------------------------------------
David Berg jest ekspertem z AZ Coagulation Services in Phoenix :
nadkrzepliwośc
Ocenił skuteczność różnych środków do leczenia nadkrzepliwości :
50% - Bromelain 50% - bromelaina
60% - Wobenzym 60% - Wobenzym
70% - Serrapeptase 70% - Serrapeptase
80% - Nattokinase 80% - Nattokinase
95% - Lumbrokinase 95% - Lumbrokinase
Czosnek, witamina E, oleje rybne i K2 mogą być pomocne przy regulacji krzepnięcia.
Awokado jest najlepszym źródłem witaminy K.
Heparyna jest lekiem, który okazał się pomocny przy leczeniu nadkrzepliwości
http://www.betterhealthguy.com/klinghardt-conference-lyme-and-other-chronic-infections
Dr C: Hypercoagulation, or thrombophilia, may be defined as reduced capillary blood flow or a greater tendency than normal for blood to coagulate, or clot. Of approximately 900 borreliosis patients that I have tested, 90 percent have hypercoagulation. Comparatively, only five percent of the general healthy population has hypercoagulation.
Treatment for hypercoagulation caused by infections is heparin, which is a blood thinner. Typically, heparin is given subcutaneously (under the skin) by injection twice a day in low doses for not more than nine months. It can also be compounded into a troche that dissolves in the mouth, but that is usually more expensive and is often less effective than injections. Symptoms that improve with heparin are pain, fatigue, cognitive problems and neurological problems. About 80 percent of borreliosis patients feel better with heparin, and it has been a safe treatment so far. One patient did develop bleeding from the rectum, but then a colonoscopy revealed a colon cancer that had not yet spread to the local lymph nodes. In other words, the heparin unmasked a hidden malignancy, so in this case the side effect was a blessing.
Heparin is not only a blood thinner, it is also anti-inflammatory, antiviral, antibacterial, and may even be anti-cancer (unproven). Therapy with heparin usually lowers the level of the coagulation components fibrinogen, fibrin, thrombin/antithrombin complexes, fragment 1+2 and Factor II activity. This is desirable, because elevated levels of these coagulation components can cause decreased capillary blood flow, if they are high enough. Capillaries are microscopic blood vessels that are about eight microns wide. A normal red blood cell, which travels through the capillaries, is about seven microns wide. When elevation of coagulation components occur, they could conceivably attach to the inside surface (endothelial surface) of capillaries, thereby narrowing them. For example, fibrinogen attached to the inside surface could make it harder for a seven-micron-wide red blood cell to squeeze through the narrowed capillary. Reduced blood flow in capillaries would in turn reduce oxygen and nutrients, and reduce removal of toxins from tissues. It stands to reason that if heparin could improve blood flow, antibiotics and hormones would be more effective because they could pass through capillaries easier.
Life is in the blood. Less blood flow means less “life,” and possibly more symptoms and diseases -- perhaps even death. Hypercoagulation is associated with other chronic diseases, not just borreliosis. It is my opinion that how hypercoagulation is treated will become a paradigm shift in medicine, once further research has been accomplished.
Hemex Laboratories in Phoenix, AZ has discovered that a number of infections, including mycoplasmas, and Borrelia Burgdorferi can trigger the blood clotting system to become active, preventing oxygen and antibiotics from reaching and destroying the pathogen. This is called hypercoagulation. The Hemex Lab ISAC panel can be run to determine if this is a problem. If this test is positive, appropriate blood thinning agents may be prescribed (Heparin is the preferred choice).
There are a number of problems that must be addressed in patients. For instance, some individuals have a coagulation defect that is set off by the chronic infection Borrelia Burgdorferi (Lyme Disease). This results in the laying down of a fibrin coating on the lumen of the vessel causing impaired oxygen and nutrient transfer. This can result in fatigue, muscle aches and "brain fog". If suspected, diagnosis requires specialized testing (presently only available at Hemex Laboratories in Phoenix) . If not treated, not only are the cells starved for oxygen and nutrients, but it is very difficult to eradicate any infection because they will "hide" in the fibrin coating. If the Coagulation defect is not addressed the defect will limit the antibiotics from reaching and destroying the pathogen
Hypercoagulation leads to "clogging" of our mucous membranes with extra Fibrin and doesn't allow for proper entry into cells of nutrients or egress from cells of waste products. Eventually this causes our interstitial fluids (Terrain) to be filled with toxic waste (Dr. Reckeweg's Homotoxins) and our cells to be deprived of proper nutrients. This leads to all forms of chronic degenerative diseases such as atherosclerosis, Fibromyalgia, arthritis, cirrhosis, emphysema, chronic fatigue and the 100 or so other chronic degenerative diseases.
Dr K: Studies have found that approximately 80% of patients have this low level activation of the clotting system. This low level activation does not produce a blood clot, but rather an intermediate substance called a soluble fibrin monomer (SFM). This coats the inside of the blood vessel and limits oxygen and nutrient flow into the cells. The SFM coating not only limits the oxygen and nutrient flow, but it also provides a place for the spirochete to "hide" and escape destruction by the immune system/antibiotic. Thus, it can be very difficult for patients to rid the body of these infection without treating the Fibrogen Defect. Diagnosis is made by the use of a specialized test called an ISAC (Immune System Activation of Clotting) panel, which measures platelet activation, soluble fibrin monomer, fibrinogen, prothrombin fragment 1 +2 and thrombin/antithrombin complexes. Treatment is low dose heparin and substances to break up the fibrin as well as elimination of the initiating agent, whether it is a virus, bacteria, yeast or toxin. Intervention can be from several weeks to a number of months, if treating with antibiotics Heparin should be continued for the duration of antibiotic treatment.
Growth-Inhibitory Effect of Heparin on Babesia Parasites There is some very current information and an actual study showing that heparin may erradicate Babesia all on it's own and the same may hold true for Lyme- Sabine Bork,1 Naoaki Yokoyama,1 Yuzuru Ikehara,2 Sanjay Kumar,1 Chihiro Sugimoto,1 and Ikuo Igarashi: We examined the inhibitory effects of three heparins on the growth of Babesia parasites. The multiplication of Babesia bovis, B. bigemina, B. equi, and B. caballi in in vitro cultures and that of B. microti in vivo were significantly inhibited in the presence of heparins, as determined by light microscopy. Treatment with various concentrations of heparin showed complete clearance of the intracellular parasites. Interestingly, a higher percentage of abnormally multidividing B. bovis parasites was observed in the presence of low concentrations of heparin. Furthermore, fluorescein isothiocyanate-labeled heparin was preferably found on the surfaces of extracellular merozoites, as detected by confocal laser scanning microscopy. These findings indicate that the heparin covers the surfaces of babesial merozoites and inhibits their subsequent invasion of erythrocytes.
----------------------------------------------------------
Interview with David Berg
David Berg is the Director and Cofounder, with Lois Hill Berg, of HEMEX Laboratories. Along with Dr. Harold Harrison and several clinical collaborators, they have developed the idea of the hypercoagulation/ immune system activation of coagulation theory in chronic diseases, a proposed cause of Chronic Fatigue Syndrome and Fibromyalgia, and have proposed an appropriate treatment that reduces many related symptoms. Mr. Berg has a M.S. degree in clinical pathology and laboratory medicine, and has been in practice for 35 years. HEMEX Laboratories offers testing and consultative services relating to the diagnosis, treatment, and monitoring of hematological, clotting and/or bleeding disorders. We first became involved with research in chronic illnesses while we were performing re search regarding hypercoagulability - related infertility in women with one of the local infertility specialists here in Phoenix, AZ. We found that a hypercoagulable state, presumably due to a coagulation protein defect, existed in many women who were infertile and/or who had recurrent spontaneous abortions. Our colleague Dr. Couvaras observed that when he put women on low dose heparin in order to maintain pregnancy, some with CFS/FM-like symptoms, pelvic pain, and migraine-like headaches had amelioration of their symptoms. He asked us ``Why?'' As a result, we performed a retrospective study on 30 of these obstetric patients with chronic illness symptoms, and determined that all had coagulation system activation. As the hypercoagulability was decreased by heparin injections, the chronic illness symptoms diminished. This was the first clue to the connection between coagulation and chronic illnesses. These findings were published as a poster at the 1998 AACFS meeting in Cambridge, MA. We subsequently refined our test panel for low level activation of coagulation to include Prothrombin fragment 1+2 (F1+2), thrombin/antithrombin complexes (T/AT) and Platelet Activation by Flow Cytometry assays. Thus, the ISAC or Immune System Activation of Coagulation panel consisting of fibrinogen (FIB), soluble fibrin monomer (SFM), F1+2, T/AT, and PA by Flow was born. With our partner and Medical Director, Dr. Harold Harrison and several clinical collaborators, we then designed and conducted a prospective, multi-center, blinded, case control, associative study of non-obstetric CFS/FM patients and controls, with centers in New York, Houston, and Phoenix. When the code was broken, identifying patients and controls, we were able to identify most of the CFS/FM patients based on having two or more positive test results out of the five assays in the ISAC panel. It was the first definitive evidence that, indeed, chronic illnesses have a demonstrable basis in the blood coagulation system. This study was published in the international journal Blood Coagulation & Fibrinolysis, 1999, 10:435-438. In another associative cohort study published in Blood Coagulation & Fibrinolysis, 2000, 11:673-678, we determined that Gulf War illness has similar findings of low level activation of coagulation. In November, 1999, Dr. Joe Brewer (an Infectious Disease specialist in Kansas City) and I developed a model of pathogen activation of the immune and coagulation systems. The model proposes that the end result of such pathogenmediated activation is increased blood viscosity due to 1) an underlying coagulation regulatory protein defect, and 2) activation of the coagulation system by the pathogen. As the blood viscosity increases, the diminished blood flow creates hypoxia (lack of oxygen) and nutrient deprivation within various areas of the body. This is like trying to start your car in Wisconsin in the winter with 60- weight engine oil. This model explains the multi-organ symptomatology and also explains why the low dose heparin therapy is effective by increasing blood flow as the blood viscosity decreases. Thus, patients gain relief from their symptoms with this therapy. The model states that coagulation activation generates thrombin, which converts fibrinogen to soluble fibrin monomer (SFM). Soluble fibrin becomes deposited in the micro-circulation (capillaries) as fibrin or fibrinoid-like deposition, blocking oxygen and nutrients transfer to parenchymal tissues. Many pathogens activate the immune system. These include viruses (such as EBV, CMV, HHV6 & others), bacteria (mycoplasma, chlamydia, borrelia, etc), fungi (such as candida), etc. These pathogens are anaerobes, i.e., they live and reproduce in an oxygen deprived cellular matrix or environment. That's why fibrin deposition becomes important to the survival of the pathogens because it produces decreased oxygen in cells and tissues. One of the biggest challenges to a clinician is to figure out what pathogens are present in the patient, and therefore the most appropriate therapies against these pathogens. The average CFS/FM patient may have anywhere from one to seven pathogens that need eradication. Positivity of two or more tests in the ISAC panel occurs in more than 80% of all patients tested. However, the longer a patient has been ill (many years), the less activation is needed by the pathogens for survival, and therefore fewer tests may be positive. Someone who has been ill for 10 years or more may only have one test positive in the panel. The ISAC panel also works very well for monitoring anticoagulant therapy between 4-6 weeks after therapy has started. It indicates whether or not there is enough heparin being given to the patient, the overall patient improvement and the reaction of the body to the pathogens, such as a Herxheimer-like reaction (relapse from infections or reactivation of pathogens). In addition to the pathogens that can activate the immune system, metals (e.g. mercury, lead, aluminum), exogenous toxins, chemicals, allergens, physical trauma, vaccinations, and/or biological warfare agents can also activate the immune system. This may lead to secondary infections, which may also trigger coagulation activation. If the coagulation mechanism does not shut down properly, then there is continued thrombin generation and soluble fibrin formation, resulting in increased blood viscosity and decreased blood flow. When you look for a genetic basis in this model, one can test for seven different regulatory proteins of the coagulation mechanism plus homocysteine in a panel we call the HTRP (Hereditary Thrombosis Risk Panel). In July 2001, at the International Society of Thrombosis and Hemostasis meeting in Paris, we presented data from a retrospective study of over 400 chronically ill patients, 83% had one or more demonstrable coagulation protein defects. Forty percent of the patients had a thrombophilia defect (decreased protein C, decreased protein S, decreased anti-thrombin, APC resistance/factor V Leiden positivity, or increased prothrombin/prothrombin gene mutation positivity). 39% of the patients have defects in the fibrinolytic system (hypofibrinolysis due to elevated lipoprotein (a) - Lp(a) and/or PAI1-plasminogen activator inhibitor-1. 21% of these patients had a defect in both the thrombophilia and hypofibrinolysis marker groups. This means that not only do they form fibrin easily, but also they are compromised in the ability to clean up the fibrin deposition. Let's put this in plain English. When a pathogen(s) gains a foothold, especially in the endothelial cells in the blood vessels (as well as other cells), the bug(s) can be protected by the coagulation mechanism of fibrin deposition on top of the infected cells. Half of the patients form fibrin very fast, becoming fibrin(oid) deposition. Half of the patients have an inability to clean up the fibrin, and therefore continue to have oxygen and nutrient starvation of tissues for a long time. For example, if the fibrin deposition occurs in a muscle, it says ``ouch,'' and you have a tender point as in Fibromyalgia. If it is in the placenta, the placenta is compromised by fibrin deposition and the baby aborts. As blood viscosity increases and blood flow is reduced throughout the body, the patient becomes hypo-this and hypo-that, such as hypothyroid, hypo-HPAaxis, hypo-estrogen, etc. The use of low dose heparin restores blood flow throughout the body and hormones from the endocrine system tend to normalize. Thus, the blood flow issue becomes one of the most important issues of chronic illnesses. Unfortunately there is no easy test to measure blood flow, only the effects of blood flow. If you consider the movie ``Braveheart'' (1000 AD) and you went to battle and were wounded, you probably would have bled to death unless you clotted fast. By clotting fast, you saved your own life and passed on this new trait to your children. This hypothesis may explain how these coagulation defects were genetically selected during the last 2000 years in Europe. Life expectancy back then was only 30-40 years. With our life expectancy now of 80+ years, these traits are no longer beneficial, but rather deleterious to our health. It was the Spanish, French, British, Germans, Italians, Scandinavians, etc. (Europeans) that colonized the Americas. This explains why most of the chronically ill patients are white people of European decent. Therefore we have a genetic basis in the coagulation system for chronic illnesses that is very straightforward.
The model of reduced blood flow from increased blood viscosity due to activation of coagulation accompanied by a coagulation protein defect gives a scientific basis for a contribution to the pathophysiology of chronic illness. It also gives a measurable or quantifiable, objective aspect to testing the blood of patients with these diseases. It is no longer ``all in your head'', but rather in your ``blood.'' It's not rocket science, but a simple, logical explanation for what's going on in many chronically ill patients.
HEMEX Laboratories provides testing services and consultative interpretations to clinicians and physicians throughout the United States. For more information, technical reprints, and/or patient information, please see their website at www. hemex.com
http://www.springboard4health.com/notebook/health_hypercoagulation_ill.html
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Hypercoagulation
The CFS/FM Plot Thickens
Melissa Kaplan, The Carousel Network News, 8(5), 2001
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A simplified introduction into hypercoagulable state...
Research conducted by Dr. David Berg and others at Hemex Laboratories1 has found hypercoagulation to be a factor in many patients with chronic fatigue syndrome (CFS), fibromyalgia (FM), myofascial pain syndrome (MPS), and other disorders such as osteonecrosis (bone loss due to inadequate blood supply), and fetal loss.
Hypercoagulation (thickened blood) results from fibrin being deposited in small blood vessels. Fibrin is the body's natural bandaid: strands of fibrin form across a defect (wound, tear) in the walls of blood vessels, forming a mesh that holds platelets and blood cells. This beneficial clotting of cellular matter and fibrin strands plugs the leak, so to speak, holding things together until the body starts to repair itself.
Fibrin production is the last stage in a complex clotting process. The process itself starts off with the release of thrombin which in turn results in the production of soluble fibrin monomer (SFM), a sticky protein that increases blood viscosity. This leads to the deposit of fibrin on the endothelial cells that line the wall of the blood vessels. Under the normal conditions, it takes only a single burst of thrombin to generate a large amount of SFM which in turns produces sufficient amounts of fibrin to clot the defect. Testing of many patients diagnosed with CFS, FM, MPS shows that the thrombin-SFM-fibrin process is not working properly. Instead of a single burst of thrombin producing the amount of SFM needed, the thrombin keeps being produced at low levels. Instead of clots being formed, however, the result is that blood becomes increasingly thickened. The body's own ability to thin blood and break up clots is impaired because the fibrin smothering the endothelial cells prevents those cells from releasing heparans.
There are two different ways this scenario can be played out. The first is thrombinphilia, "thrombin loving", where the body keeps producing thrombin because the normal control that would prevent excessive or inappropriate thrombin generation fail, do not exist, or have somehow been overridden so the body keeps producing thrombin at low levels. The controller is anti-thrombin (AT). AT combines with thrombin to form thrombin/anti-thrombin (T/AT). Normally, when the endothelial cells release heparans, the release activates the AT, which acts slowly to reduce the thrombin. Not enough AT may be produced, or the amount may not be enough to keep up with the continuous thrombin production. Another possible cause is hypofibrinolysis, where too little heparans, the body's natural clot busters, is produced or circulated. So, in the (simplified) three part process (thrombin, antithrombin, heparans), one or more parts is dysregulated or rendered insufficient, leading to hypercoagulation.
Berg states that there are at least three possible causes for this thrombin malfunction:
The results of this thickened blood are widespread, due to the role blood plays as the major transport of nutrients and oxygen throughout the body:
Some of the symptoms associated with hypercoagulation will surprise few with CFS and/or FM: brainfog, cognitive dysfunction, digestion problems, fatigue, and generalize malaise.
Because this hypercoagulability does not result in an immediate thrombosis (100% occlusion), but rather in fibrin deposition (50-95%), Berg, et al.2 suggest that an appropriate name for this antiphospholipid antibody process would be Immune System Activation of Coagulation (ISAC) syndrome.
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Dr. Cheney says that Immune System Activation of Coagulation, called hypercoagulation, needs to be dealt with early on or other chronic fatigue treatments may not be effective. In hypercoagulation, pathogens and/or toxins activate the immune system to lay down fibrin in blood vessels. The fibrin coats the walls, blocking oxygen and nutrients from getting to nearby tissues. Researchers found that 80% of patients with an autoimmune illness had this coagulation. So this condition undoubtedly is common in chronic fatigue. Pathogens that activate this include viruses, bacteria (mycoplasma, chlamydia, etc.) and fungi (such as candida). These pathogens are anaerobes, they live in an oxygen deprived environment. And are infections common with chronic fatigue. Fibrination helps them survive because it causes decreased oxygen. And the less oxygen the better for them. Unfortunately, this can cause a great deal of damage in chronic fatigue. Everything from decreased energy to a buildup of toxins and lactic acid in cells. Hypercoagulation is not an accurate name for this condition as it is not that the blood is too thick. It is that the capillaries become coated with fibrin and the blood cannot flow freely. Fortunately, fibrin can be cleaned off artery walls. Using, of all things, digestive enzymes. Here’s why they can help. If you take a digestive enzyme on an empty stomach, so that it has nothing to digest in the stomach, the enzymes get into the bloodstream. (Many studies prove enzyme supplements do this.) Once there, they may do several things, break down partially digested food, kills pathogens, and clean up the blood in general. Including toxins produced by mycoplasma or any of the other toxin producing micro-organisms. More important for hypercoagulation, enzymes may clean the walls of the blood vessels. Digesting and breaking down fats, and in the case of chronic fatigue hypercoagulation, the fibrin (a protein) that coats the walls. There is another aspect to this. Mycoplasma and viral infections may cause blood cells to stick together. Called cold algination. Sticky clumps of red blood cells cause problems. Oxygen and nutrients can’t get to cells efficiently when red blood cells are clumped up. The cells get stuck in small capillaries and clog them up. Seriously reducing oxygenation to cells. I have heard from nutritionists who use enzyme supplements to clean blood, that taking a good quality enzyme high in protease and lipase on an empty stomach will work to unstick those red blood cells within a short period of time. So take digestive enzymes between meals and with meals. They help take a strain off the immune system because fewer partially digested food particles will enter the bloodstream. When you can’t digest food completely, partially digested food can make its way into the bloodstream. Where it can act as toxins and literally cause the immune system to devote energy and resources to cleaning it up. In addition this can cause, in many cases, food allergies to develop. This is especially true if you have a candida infection that is eating holes in your intestinal walls, thereby allowing partially digested food to enter the bloodstream. Enzymes between meals may help clean up this mess. The best enzyme to do this job, is Bromelain:}
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Understanding Chronic Fatigue Syndrome
by Robert HarrisonPart 2 Hypercoagulation, Enzymes Dr. Cheney says that Immune System Activation of Coagulation, called hypercoagulation, needs to be dealt with early on or other chronic fatigue treatments may not be effective. In hypercoagulation, pathogens and/or toxins activate the immune system to lay down fibrin in blood vessels. The fibrin coats the walls, blocking oxygen and nutrients from getting to nearby tissues. Researchers found 80% of patients with an autoimmune illness had this coagulation. Pathogens that activate this include viruses, bacteria (mycoplasma, chlamydia, etc.) and fungi (such as candida). These pathogens are anaerobes, they live in an oxygen deprived environment and are infections common with chronic fatigue. Fibrination helps them survive because it causes decreased oxygen. Unfortunately, this can cause a great deal of damage in chronic fatigue. Everything from decreased energy to a buildup of toxins and lactic acid in cells. Hypercoagulation is when the capillaries become coated with fibrin and the blood cannot flow freely. Fortunately, fibrin can be cleaned off artery walls using digestive enzymes. I f you take a digestive enzyme on an empty stomach, so it has nothing to digest in the stomach, the enzymes get into the bloodstream. Once there, they can break down partially digested food, kill pathogens, and clean up the blood in general from toxins. So enzymes play an important role in the digestion process especially in the case of chronic fatigue. There is another aspect to this. Mycoplasma and viral infections may cause blood cells to stick together which is called cold algination. Oxygen and nutrients can’t get to cells efficiently when red blood cells get stuck in small capillaries and clog them up. Enzyme supplements high in protease and lipase on an empty stomach will work to unstick those red blood cells within a short period of time. Therefore it makes sense to take digestive enzymes between meals and with meals to help take a strain off the immune system.
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Hypercoagulation means thickened blood. Research from the late 1990s reveals that many patients with chronic disease may have an underlying coagulation defect contributing to their symptoms. While few doctors are familiar with this condition, understanding the theory behind it can help explain many symptoms. Treatment based on this theory can lead to improvement and even recovery.
David Berg of Hemex Laboratories has been studying the hypercoagulation often found in patients with chronic disease. This list currently includes CFS/FMS, myofascial pain syndrome, osteonecrosis of the jaw, fetal loss, multiple sclerosis, Crohn's disease, Sjogren's syndrome, IBS, Lyme disease, autism, gulf war illness and ADD.Thick blood is the result of fibrin being deposited in the small blood vessels. Fibrin formation is the last step in the clotting process that stops bleeding when blood vessels are cut. Normally, long strands of fibrin weave a mesh around platelets and blood cells to form a clot that plugs the break in the wall of a vessel.A very complex series of reactions activates the clotting process. The release of thrombin ultimately results in the production of a substance called soluble fibrin monomer (SFM). SFM is a sticky protein that increases blood viscosity (thickness) and results in the deposit of fibrin on the endothelial cells lining the blood vessels. Normally, a single burst of thrombin would generate a large amount of SFM that would produce strands of "cross linked" fibrin, resulting in an actual clot. However, in CFS/FMS and other chronic conditions, continuous generation of low levels of thrombin can occur. The result is hypercoagulation. There are at least three possible causes or contributing factors:Virii, bacteria, mycoplasmas, and/or parasites activate certain antibodies in the immune system that trigger the production of thrombin, generate SFM and result in fibrin deposits.Genetic coagulation defects can lead to hypercoagulation. White people are susceptible to this and black people have a resistance to it. Chemical exposure can result in changes that trigger the coagulation process. The results of this thickened blood are: When fibrin coats the walls of the capillaries, nutrient and oxygen delivery to muscle, nerve, bone and organ tissue is compromised. The fibrin coating the capillaries and producing thick blood can make virii and bacteria less accessible to treatment. Thicker blood is harder to pump. By depriving the gut of proper nourishment, hypercoagulation may be a major factor in IBS. If the bowel is deprived of blood, cells will die too rapidly. The endothelial cells lining the capillaries are the source of heparans, the body's natural blood thinners. When fibrin coats these cells, the heparans cannot be released, reducing the body's ability to dissolve the fibrin. Hypercoagulation can be detected by Hemex Laboratories' ISAC (Immune System Activation of Coagulation) test panel. Five substances are measured, and abnormal results on any two are considered a positive test result. A standard coagulation work up usually will not detect any abnormalities, since it only assesses the risk of actual clotting. The ISAC panel is 10 to 20 times more sensitive, as well as being more expensive. In a 1998 study, heparin was given to 7 FMS and 9 CFS patients suffering from hypercoagulation. Of the 7 FMS patients, 1 reported some, 3 moderate, and 3 significant improvement. Of the 9 CFS patients, 4 reported moderate and 5 significant improvement.Since then, David Berg has learned that the best chance of success involves treating both the hypercoagulation and the underlying pathogen(s). Ideally, a blood thinner such as heparin is prescribed one month before beginning antibiotics for bacteria (for example mycoplasma or chlamydia pneumonia) and/or transfer factor for viruses (such as HHV6, CMV and EBV). The heparin is continued throughout, and then slightly beyond, the course of anti-microbial treatment. It dissolves the fibrin, making the virus and/or bacteria more vulnerable, thus improving the treatment's effectiveness.CFS/FMS patients who have been ill for more than ten years may show only one abnormality - or possibly none - on the ISAC test. A trial of heparin, however, especially if accompanied by antibiotics or transfer factor, may change that. Berg suspects that once a pathogen has a large area of fibrin deposits in which to settle, the less active it needs to be. It may therefore stop triggering the coagulation process. As the heparin removes the fibrin and allows a more effective attack against the pathogens, they reactivate and/or become more active, once again triggering the coagulation process. Most patients have more abnormalities on the ISAC test one month into treatment than on their initial test, indicating progress. They often must pass through a time of increased illness when the infection is temporarily activated. The treatment of this condition is not easy or inexpensive. It requires a doctor who is familiar with the theory, comfortable with the lab testing and willing to individualize treatment. There is more info in this article that can be viewed on the site. There are also links to conditions that may be related. http://www.diagnose-me.com/cond/C546624.html ---------------------------------------------------------- by Robert Harrison Hypercoagulation, EnzymesDr. Cheney says that Immune System Activation of Coagulation, called hypercoagulation, needs to be dealt with early on or other chronic fatigue treatments may not be effective. In hypercoagulation, pathogens and/or toxins activate the immune system to lay down fibrin in blood vessels. The fibrin coats the walls, blocking oxygen and nutrients from getting to nearby tissues. Researchers found 80% of patients with an autoimmune illness had this coagulation. Pathogens that activate this include viruses, bacteria (mycoplasma, chlamydia, etc.) and fungi (such as candida). These pathogens are anaerobes, they live in an oxygen deprived environment and are infections common with chronic fatigue. Fibrination helps them survive because it causes decreased oxygen. Unfortunately, this can cause a great deal of damage in chronic fatigue. Everything from decreased energy to a buildup of toxins and lactic acid in cells. Hypercoagulation is when the capillaries become coated with fibrin and the blood cannot flow freely. Fortunately, fibrin can be cleaned off artery walls using digestive enzymes.If you take a digestive enzyme on an empty stomach, so it has nothing to digest in the stomach, the enzymes get into the bloodstream. Once there, they can break down partially digested food, kill pathogens, and clean up the blood in general from toxins. So enzymes play an important role in the digestion process especially in the case of chronic fatigue.There is another aspect to this. Mycoplasma and viral infections may cause blood cells to stick together which is called cold algination. Oxygen and nutrients can't get to cells efficiently when red blood cells get stuck in small capillaries and clog them up.Enzyme supplements high in protease and lipase on an empty stomach will work to unstick those red blood cells within a short period of time. Therefore it makes sense to take digestive enzymes between meals and with meals to help take a strain off the immune system.Lack Of Oxygen In CFSLack of oxygen, at the cellular level, may cause many problems in chronic fatigue. Decreased oxygen to the left side of the brain can result in the short term memory loss -- so common in chronic fatigue. Also the long term malfunctioning of some glandular and hormonal systems in the brain may be effected.Low oxygen also equates to low energy which may be one reason CFS patients have cold fingers and/or feet.Oxygen is also needed to oxidize and detoxify toxins. When cells don't have enough oxygen, they may not be able to detoxify themselves adequately.Benefits Of OxygenOxygen kills anaerobic bacteria, mycoplasma and viruses. It works so well it is used to purify water through Ozonation. As people with chronic fatigue need more oxygen than someone without CFS.Many believe in oxygen supplements; however, they lack an effective delivery system. They have no way to get oxygen into the cells. http://www.inlightimes.com/archives/2003/06/chronic-fatigue3.htm -------------------------------------------------------------------------------------Getting enough oxygen into the cells is key in helping with the whole range of chronic fatigue caused oxygen deficiencies.Detoxification And Free Radical Damage In Chronic FatigueThe problems in CFS run much deeper than a messed up immune system, wiped out enzymes, oxygen depleted cells or unfriendly pathogens.When the liver can't effectively detoxify the body major health challenges can occur.People with CFS slowly become toxic, storing away poisons in fatty tissue, muscles, organs and the brain.Dr. Cheney explains that fatigue becomes worse. Pain increases. You feel sicker. Memory suffers as the brain is damaged by toxins and free radicals, and not enough oxygen gets into the brain. Deep brain structures like the hypothalamus eventually are injured and cause problems with virtually every hormone in your body. They lose their ability to rise and fall according to signals or demands from the body making it harder to respond to changing situations. Actual damage to the DNA of the energy producing mitochondria can occur.For the reasons stated in this article, if is very important to take seriously the ramifications of Chronic Fatigue Syndrome.------------------------------------------------------------Klinghardt o Rechts-regulat hipercoagulation. Wg niego działa na babesję i mykoplazme. Anergy - the absence of reaction due to the successful evasion of the host-defenses. One of the more known mechanisms the microbes use to create anergy is hyper coagulation. The microbes tend to live in the endothelium, where the food is most abundant. They trigger the host’s coagulation mechanism to lay down a layer of fibrin on top of them to evade recognition by the immune system, etc. For this aspect we use three techniques: a) the KMT-microcurrent technology and homeopathics to wake up and entrain the immune system b) Rechtsregulat “right rotatory fluid” which is an enzyme rich extract of fermented fruits and vegetables (14). It has outperformed the s.c. injection of heparin in our own trials and frequently leads to rapid subjedtive improvement.Lumbrokinase is far more effective then Nattokinase. Both appear weak when compared to Rechtsregulat. We also work on recognizing and eliminating those factors that block the client’s system (geopathic stress, EM stress, food allergies, emotional factors, interference fields such as scars and disturbed ganglia and we substitute vitamins and minerals based on ART testing). c) the Enderlein remedies (especially the haptens) from Pleomorphic-Sanum ---------------------------- G. Mycoplasma responds well to enzymes, when it is treated in sequence with the other microbes as outlined here. The most effective strategy is the German product Rechtsregulat (14). This simple drink has been extremely effective in eradicating mycoplasma and other cell wall deficient microbes.It also has a heparin like anti-fibrin effect that surpasses injected heparin by far. It has just like heparin, a strong biological effect against Babesia as well. Dosage: 1 tbs/2 times per day in a glass of water. Either add the daily dose of Rechtsregulat (acidic ph) into the bottle or take on empty stomach, when stomach-ph is low. ------------------------------------- Growth-inhibitory effect of heparin on Babesia parasites. Abstract
We examined the inhibitory effects of three heparins on the growth of Babesia parasites. The multiplication of Babesia bovis, B. bigemina, B. equi, and B. caballi in in vitro cultures and that of B. microti in vivo were significantly inhibited in the presence of heparins, as determined by light microscopy. Treatment with various concentrations of heparin showed complete clearance of the intracellular parasites. Interestingly, a higher percentage of abnormally multidividing B. bovis parasites was observed in the presence of low concentrations of heparin. Furthermore, fluorescein isothiocyanate-labeled heparin was preferably found on the surfaces of extracellular merozoites, as detected by confocal laser scanning microscopy. These findings indicate that the heparin covers the surfaces of babesial merozoites and inhibits their subsequent invasion of erythrocytes.
Babesia parasites are tick-transmitted intraerythrocytic protozoa of the phylum Apicomplexa. They affect a wide variety of wild and domestic animals and are responsible for enormous economic losses to the livestock industry worldwide (25). Moreover, some are major etiologic agents of human babesiosis (20). During the asexual growth cycle in a natural host, merozoites internalize the host erythrocytes (RBCs) via multiple adhesive interactions of several protozoan molecules with the host cell surface (45). Thus, the parasites destroy the infected RBCs, which results in severe clinical symptoms, such as high fever, anemia, hematuria, and hemoglobinuria, in the infected hosts. Therefore, understanding of the basic molecular mechanism(s) of the asexual growth cycle, particularly the process of merozoite invasion into the host RBC, may accelerate the development of effective therapeutic methods and methods for the prevention of babesiosis.
Heparin is a highly sulfated form of heparan sulfate (HS) (36) and is known to be an inhibitor of the blood coagulation system (19, 23) or as a coreceptor in the binding of fibroblast growth factor to its receptor (29). HS and heparin are complex entities composed of anionic, linear mucopolysaccharides with alternating uronic acid and hexosamine residues in which a limited set of monosaccharide units gives rise to a number of complex sequences by variable substitution with O-sulfate, N-sulfate, and N-acetyl groups (28), rendering the heparin polydisperse (26). While HS is produced in most cell types, heparin is a biosynthetically derived component of mast cells and basophils (16) and has a molecular weight (MW) of approximately 3,000 to 37,500, with an average MW of 13,000 (26). Due to the sulfate and carboxylate residues, heparin is highly negatively charged (9) and, moreover, is often used as a model glycosaminoglycan (GAG) to study the HS interaction with proteins (29).
Heparin has also been used for the treatment of patients affected by the cerebral form of Plasmodium falciparum infection (27, 30, 39). The therapeutic effect of heparin was demonstrated in rhesus monkeys experimentally infected with Plasmodium knowlesi (11). The growth-inhibitory effects of heparin were also described in in vitro studies with P. falciparum (7, 24, 38) and Theileria sergenti (14). However, the precise mechanisms of its inhibitory capacity against these hemoprotozoa are not fully understood.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC310193/  |
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