1. CLOTTING DISORDERS (HERIDETARY)

2. INHERITED HEPERCOAGULAABILITY STATE. ANTITHROMBIN III DIFICIENCY. ANTITHROMBIN III DIFICIENCY. PROTEIN S DIFICIENCY PROTEIN S DIFICIENCY PROTEIN C DIFICIENCY PROTEIN C DIFICIENCY ACTIVATED PROTEIN C-RESISTANCE ACTIVATED PROTEIN C-RESISTANCE HEPARIN COFACTOR DIFICIENCY HEPARIN COFACTOR DIFICIENCY DISPLASMINOGENAEMIA DISPLASMINOGENAEMIA PLASMINOGEN ACTIVATOR DIFICIENCY PLASMINOGEN ACTIVATOR DIFICIENCY PLASMINOGEN ACTIVATOR INHIBITOR EXCESS PLASMINOGEN ACTIVATOR INHIBITOR EXCESS

3. Thrombosis and thrombophilia Thrombosis is a specific medical term given for the formation of a blood clot (thrombus) inside a blood vessel, obstructing the flow of blood through the circulatory system. Thrombosis is a specific medical term given for the formation of a blood clot (thrombus) inside a blood vessel, obstructing the flow of blood through the circulatory system. Thrombosis is resulting in ischaemia, which means deficiency of blood in a part, due to actual obstruction of a blood vessel e.g. Myocardial infarction and deep vain thrombosis. Thrombosis is resulting in ischaemia, which means deficiency of blood in a part, due to actual obstruction of a blood vessel e.g. Myocardial infarction and deep vain thrombosis.

4. Thrombophilia = tendency of thrombosis Thrombophilia = tendency of thrombosis Thrombosis is classified into arterial and venous thrombosis. Thrombosis is classified into arterial and venous thrombosis. The thrombus may be subsequently lysed by fibrinolysis. The thrombus may be subsequently lysed by fibrinolysis. It becomes more common with age. It becomes more common with age.

5. Causes In classical terms, thrombosis is caused by abnormalities in one or more of the following (Virchow's triad, who is a German physician and pathologist): In classical terms, thrombosis is caused by abnormalities in one or more of the following (Virchow's triad, who is a German physician and pathologist):Virchow 1. The composition of the blood (hypercoagulability) caused for example, by genetic deficiencies or autoimmune disorders. 2. Damage of the vessel wall (endothelial cell injury) such as by trauma or infection. 3. Slowing down of the blood flow (hemostasis) past the point of injury (which may occur after long periods of sedentary behavior - for example, sitting on a long airplane flight). High altitude has also been known to induce thrombosis. High altitude has also been known to induce thrombosis. Intravascular coagulation follows, forming a mass of red blood cells, leukocytes, and fibrin. Intravascular coagulation follows, forming a mass of red blood cells, leukocytes, and fibrin.

6. Classification OF THROMBOSIS There are two distinct forms of thrombosis: There are two distinct forms of thrombosis: 1. Arterial thrombosis : A blood clot within an artery is known as an arterial thrombosis. 2. Venous thrombosis

7. The causes of arterial thrombosis: Arterial thrombosis usually affects individuals who already have: Arterial thrombosis usually affects individuals who already have: Atherosclerosis, or narrowing of the arteries. Atherosclerosis, or narrowing of the arteries. Stroke Stroke Myocardial infarction Myocardial infarction Myocardial infarction Myocardial infarction

8. Risk factors for arterial thrombosis The main risk factors for arterial thrombosis include: The main risk factors for arterial thrombosis include: Smoking Smoking High blood pressure High blood pressure Increased levels of cholesterol Increased levels of cholesterol Diabetes Diabetes Increasing age Increasing age Family history Family history Poor diet Poor diet Excess body weight Excess body weight Physical inactivity. Physical inactivity. Of these, the major risk factors are smoking, high blood pressure (hypertension), and increased cholesterol levels. Of these, the major risk factors are smoking, high blood pressure (hypertension), and increased cholesterol levels.

9. Symptoms of arterial thrombosis The symptoms will very according to the affected site. The symptoms will very according to the affected site. For example, in MI, A number of clinical findings can be preceded including high blood pressure and angina. For example, in MI, A number of clinical findings can be preceded including high blood pressure and angina. The symptoms of angina include chest pain during exercise or when feeling emotional stress The symptoms of angina include chest pain during exercise or when feeling emotional stress

10. 2- Venous thrombosis A venous thrombosis is a blood clot that forms within a vein. A venous thrombosis is a blood clot that forms within a vein.blood clotveinblood clotvein Superficial venous thromboses can cause discomfort but generally do not cause serious consequences, unlike the deep venous thromboses (DVTs) that form in the deep veins of the legs or in the pelvic veins. Superficial venous thromboses can cause discomfort but generally do not cause serious consequences, unlike the deep venous thromboses (DVTs) that form in the deep veins of the legs or in the pelvic veins.deep venous thrombosesdeep venous thromboses

11. Risk factors General General Older age Older age Female gender Female gender Smoking Smoking Obesity Obesity Pregnancy PregnancyMedical Surgery Surgery Trauma Trauma Oral contraceptive use Oral contraceptive use Malignancy Malignancy Kidney disorders Kidney disorders Lupus anticoagulant Lupus anticoagulant PNH DIC Familial Familial Antithrombin III deficiency Protein C deficiency/Protein S deficiency Protein C deficiency APC resistance (Factor V Leiden) Familial homocysteinemia

12. Thrombophilia It is a term used to describe both: the inheritance and acquired haemostatic disorders which predispose to thrombosis. It is a term used to describe both: the inheritance and acquired haemostatic disorders which predispose to thrombosis. It is classified into inherited and acquired thrombophilia. It is classified into inherited and acquired thrombophilia. Inherited thrombophilia: Mentioned in the beginning of the lec. Mentioned in the beginning of the lec. Presentation may be during early child-hood or in adulthood, e.g. at commencement of oral contra­ceptives. Presentation may be during early child-hood or in adulthood, e.g. at commencement of oral contra­ceptives.

13. Lupus anticoagulant syndrome

14. Despite its name, this syndrome usually presents with arterial or venous thrombosis or recurrent miscarriages due o placenta infarction. Despite its name, this syndrome usually presents with arterial or venous thrombosis or recurrent miscarriages due o placenta infarction. It may be associated with systemic lupus erythematosus or other connective tissue disorders, with malignancy or infections or the idiopathic. It may be associated with systemic lupus erythematosus or other connective tissue disorders, with malignancy or infections or the idiopathic. Patients may show a spectrum of antibodies which interfere with phospholipid-dependent coagulation tests in vitro and/or react with cardiolipin. Patients may show a spectrum of antibodies which interfere with phospholipid-dependent coagulation tests in vitro and/or react with cardiolipin. The A PTT is prolonged and not corrected by a 5o:50 mix of normal plasma in patient plasma. The A PTT is prolonged and not corrected by a 5o:50 mix of normal plasma in patient plasma. Anticoagulant therapy is needed for patients with thrombosis. Anticoagulant therapy is needed for patients with thrombosis.

16. CLOTTING DISORDERS II Acquired 1. Liver disease 2. Vitamin K deficiency 3. Disseminated Intravascular Coagulation 4. Coumadin therapy 5. Heparin therapy

17. 1-Liver disease Liver disease leads to defects of coagulation, platelets and fibrinolysis: Liver disease leads to defects of coagulation, platelets and fibrinolysis: 1. Reduced synthesis of vitamin K dependent factors caused by impaired vitamin K absorption. 2. Impaired synthesis of other coagulation proteins (factor I and V ). 3. Thrombocypenia {hypersplenism) and abnormal platelet function (cirrhosis). 4. Fibrinolysis impaired: Reduced levels of proteins C and S. antithromhin and, antiplasmin. Reduced levels of proteins C and S. antithromhin and, antiplasmin. Increased PT, aPTT, TT Increased PT, aPTT, TT

18. 2- Disseminated intravascular coagulation -DIC-

19. Definition of DIC: “A dynamic pathologic process triggered by activation of the clotting cascade with resultant generation of excess thrombin within the vascular system that leads to further activation of the coagulation system, shortened survival of certain hemostatic elements, deposition of fibrin in the micro-circulation and activation of the fibrinolytic system.” “A dynamic pathologic process triggered by activation of the clotting cascade with resultant generation of excess thrombin within the vascular system that leads to further activation of the coagulation system, shortened survival of certain hemostatic elements, deposition of fibrin in the micro-circulation and activation of the fibrinolytic system.” DIC is not a primary disorder but it is a secondary expression of an underlying process. DIC is not a primary disorder but it is a secondary expression of an underlying process.

20. DIC is seen in association with a number of well-defined clinical situations, including sepsis, major trauma, and abruptio placenta, and with laboratory evidence of the following: DIC is seen in association with a number of well-defined clinical situations, including sepsis, major trauma, and abruptio placenta, and with laboratory evidence of the following: 1. Procoagulant activation 2. Fibrinolytic activation 3. Inhibitor consumption 4. Biochemical evidence of end-organ damage or failure DIC occurs in acute and chronic forms. DIC occurs in acute and chronic forms. Also called consumptive coagulopathy. Also called consumptive coagulopathy.

21. Clinical features Both bleeding and thrombosis may occur. Both bleeding and thrombosis may occur. Tissue damage caused by thrombosis leads to necrosis and further activation of coagulation and fibrinolysis. Tissue damage caused by thrombosis leads to necrosis and further activation of coagulation and fibrinolysis. Purpura, ecchymoses, gastrointestinal bleeding. Purpura, ecchymoses, gastrointestinal bleeding. Bleeding from intravenous sites and following venepuncture may occur as a result of low levels of coagulation factors and platelets resulting from increased consumption. Bleeding from intravenous sites and following venepuncture may occur as a result of low levels of coagulation factors and platelets resulting from increased consumption. Renal function may be impaired due to microvascular thrombosis. Renal function may be impaired due to microvascular thrombosis.

22. Etiology There are a variety of causes of DIC, all usually causing the release of chemicals into the blood that activates the coagulation. There are a variety of causes of DIC, all usually causing the release of chemicals into the blood that activates the coagulation. 1. Infections: Sepsis, particularly with gram-negative bacteria Sepsis, particularly with gram-negative bacteria Sepsisgram-negative bacteria Sepsisgram-negative bacteria Viral Viral Malaria Malaria Malaria Rickettsial Rickettsial Rickettsial 1. Obstetric complications (most common cause), with chemicals from the uterus being released into the blood. uterus 2. Tissue trauma such as burns, accidents, surgery, heat stroke or shock. shock 3. Liver disease Liver 4. Incompatible blood transfusion reactions or massive blood transfusion (when more than the total circulatory volume is transfused) transfusion reactionsblood transfusion reactionsblood transfusion 5. Graft-versus-host disease Graft-versus-host disease Graft-versus-host disease 6. Cancers 7. Viral hemorrhagic fevers. Viral hemorrhagic fevers Viral hemorrhagic fevers 8. Envenomation by some species of venomous snakes. speciesvenomous snakesspeciesvenomous snakes

23. Laboratory Findings Decreased platelet count Decreased platelet count Prolonged PT, PTT, TCT Prolonged PT, PTT, TCT Decreased fibrinogen Decreased fibrinogen Elevated FDPs or D-dimers (which are produced when fibrin undergoes degradation when blood clots are dissolved by fibrinolysis). Elevated FDPs or D-dimers (which are produced when fibrin undergoes degradation when blood clots are dissolved by fibrinolysis).fibrinolysis Fragmented erythrocytes – microangiopathic hemolytic anemia Fragmented erythrocytes – microangiopathic hemolytic anemia

24. Although numerous blood tests are often performed on patients prone to DIC, the important measures are: full blood count (especially the platelet count), fibrin degradation products or D-dimer tests (markers of fibrinolysis), bleeding time and fibrinogen levels. Although numerous blood tests are often performed on patients prone to DIC, the important measures are: full blood count (especially the platelet count), fibrin degradation products or D-dimer tests (markers of fibrinolysis), bleeding time and fibrinogen levels.blood testsfull blood countplateletfibrin degradation productsD-dimerfibrinolysisbleeding time fibrinogenblood testsfull blood countplateletfibrin degradation productsD-dimerfibrinolysisbleeding time fibrinogen

25. OtherPlateletsTTAPTTPT Dysfibrinogenaemia1-N/TTTLiver disease FDP T ±RBC fragments on blood film 1-TTTDIC NNTor NT Vitamin K deficiency NTT Massive transfusion NNTT Oral anticoagula nts Anti-Xa I N (rarely1) TTTHeparin

26. Treatment The prognosis for those with DIC, depending on its cause, is often grim (bad), leading the initials to be known colloquially as "death is coming". The prognosis for those with DIC, depending on its cause, is often grim (bad), leading the initials to be known colloquially as "death is coming". Treat the underlying disease Treat the underlying disease Intensive supportive care Intensive supportive care Repletion of consumed factors Repletion of consumed factors FFP FFP Cryoprecipitate for low fibrinogen Cryoprecipitate for low fibrinogen Platelets for thrombocytopenia Platelets for thrombocytopenia Heparin Heparin ATIII Concentrates - for some indications ATIII Concentrates - for some indications

27. Other acquired disorders of coagulation 1. Drugs 2. Acquired coagulation inhibitors 3. Vitamin K deficiency Vitamin K is required to activate factors II, VII, IX and X and protein C and S. Vitamin K is required to activate factors II, VII, IX and X and protein C and S. Treatment: Replacement Vitamin K Treatment: Replacement Vitamin K Response within 24-48 hours Response within 24-48 hours 4. Haemorrhagic disease of the newborn Newborn infants are at an increased risk of bleeding because of hepatic immaturity and low levels of vitamin K. Newborn infants are at an increased risk of bleeding because of hepatic immaturity and low levels of vitamin K. It is normal to give an injection of vitamin K (1 mg) to all newborn infants in the UK. It is normal to give an injection of vitamin K (1 mg) to all newborn infants in the UK.

29. Protein C

31. Protein C is a major physiological anticoagulant. Protein C is a major physiological anticoagulant.anticoagulant It is a vitamin K-dependent serine protease enzyme, that is activated by thrombin into activated protein C (APC). It is a vitamin K-dependent serine protease enzyme, that is activated by thrombin into activated protein C (APC).vitamin Kserine protease enzymethrombinvitamin Kserine protease enzymethrombin The activated form (with protein S and phospholipid as a cofactor) degrades Factor Va and Factor VIIIa. The activated form (with protein S and phospholipid as a cofactor) degrades Factor Va and Factor VIIIa.protein ScofactorFactor VaFactor VIIIaprotein ScofactorFactor VaFactor VIIIa The protein C pathway’s key enzyme, activated protein C, provides physiologic antithrombotic activity and exhibits both anti-inflammatory. The protein C pathway’s key enzyme, activated protein C, provides physiologic antithrombotic activity and exhibits both anti-inflammatory.anti-inflammatory

32. The Protein C Anticoagulant Pathway: Thrombin escaping from a site of vascular injury binds to its receptor thrombomodulin (TM) on the intact cell surface. Thrombin escaping from a site of vascular injury binds to its receptor thrombomodulin (TM) on the intact cell surface. As a result, thrombin loses its procoagulant properties and instead becomes a potent activator of protein C. As a result, thrombin loses its procoagulant properties and instead becomes a potent activator of protein C. Activated protein C (APC) functions as a circulating anticoagulant, which specifically degrades and inactivates the phospholipid- bound factors Va and VIIIa. Activated protein C (APC) functions as a circulating anticoagulant, which specifically degrades and inactivates the phospholipid- bound factors Va and VIIIa. This effectively down-regulates the coagulation cascade and limits clot formation to sites of vascular injury. This effectively down-regulates the coagulation cascade and limits clot formation to sites of vascular injury. T = Thrombin, PC= Protein C, Activated Protein C= APC, PS= Protein S T = Thrombin, PC= Protein C, Activated Protein C= APC, PS= Protein S

33. Protein C deficiency Protein C deficiency is a rare genetic feature that predisposes to venous thrombosis and habitual abortion. Protein C deficiency is a rare genetic feature that predisposes to venous thrombosis and habitual abortion.venousthrombosishabitual abortionvenousthrombosishabitual abortion The disease belongs to a group of genetic disorders know as thrombophilias. The disease belongs to a group of genetic disorders know as thrombophilias.thrombophilias Activated protein C resistance is the inability of protein C to cleave factors V and/or VIII. Activated protein C resistance is the inability of protein C to cleave factors V and/or VIII. Activated protein C resistance Activated protein C resistance There are two main types of protein C mutations that lead to protein C deficiency: There are two main types of protein C mutations that lead to protein C deficiency: 1. Type I: Quantitative 2. Type II: Qualitative

35. Protein S. Protein S is a vitamin K-dependent plasma glycoprotein synthesized in the liver. Protein S is a vitamin K-dependent plasma glycoprotein synthesized in the liver.vitamin Kglycoproteinvitamin Kglycoprotein In the circulation, Protein S exists in two forms: a free form and a complex form bound to complement protein C4b In the circulation, Protein S exists in two forms: a free form and a complex form bound to complement protein C4bcomplement

36. Function The best characterized function of Protein S is its role in the anti coagulation pathway, it functions as a cofactor to Protein C in the inactivation of Factors Va and VIIIa. The best characterized function of Protein S is its role in the anti coagulation pathway, it functions as a cofactor to Protein C in the inactivation of Factors Va and VIIIa.coagulation Protein CFactors VaVIIIacoagulation Protein CFactors VaVIIIa Only the free form has cofactor activity. Only the free form has cofactor activity. The property of Protein S enhances the phagocytosis of the apoptotic cell, allowing it to be removed 'cleanly' without any symptoms of tissue damage such as inflammation occurring. The property of Protein S enhances the phagocytosis of the apoptotic cell, allowing it to be removed 'cleanly' without any symptoms of tissue damage such as inflammation occurring. inflammation

37. Protein S deficiency Protein S deficiency is a disorder associated with increased risk of venous thrombosis. Protein S deficiency is a disorder associated with increased risk of venous thrombosis.venous thrombosisvenous thrombosis Decreased (antigen) levels or impaired function (activity) of protein S, leads to decreased degradation of factor Va and factor VIIIa and an increased propensity (tendency) to venous thrombosis. Decreased (antigen) levels or impaired function (activity) of protein S, leads to decreased degradation of factor Va and factor VIIIa and an increased propensity (tendency) to venous thrombosis.protein Sfactor Vafactor VIIIaprotein Sfactor Vafactor VIIIa Type of Protein S deficiency: Type of Protein S deficiency: Hereditary Hereditary Acquired Acquired

38. Protein S deficiency can be acquired due to : Protein S deficiency can be acquired due to : 1. Vitamin K deficiency or Treatment with warfarin which generally also impairs the coagulation system itself (factors II, VII, IX and X), and therefore predisposes to bleeding rather than thrombosis. warfarin bleeding warfarin bleeding 2. Systemic sex hormone therapy and pregnancy 3. Liver disease and certain chronic infections (for example HIV).

39. Some characteristics of protein C system components. Further information component Neutralizes Va and VIIIa, enhances fibrinolysis, Protein C Potentiates action of thrombin on protein C Thrombomodulin Promotes protein C binding to platelets phospholipids Protein S Inhibits protein C Activated PC inhibitor Binds protein S in an inactive form. C4B- binding protein

41. Factor V Leiden mutation Factor V Leiden (sometimes Factor VLeiden) is the name given to a variant of human factor V that causes a hypercoagulability disorder. Factor V Leiden (sometimes Factor VLeiden) is the name given to a variant of human factor V that causes a hypercoagulability disorder.factor V hypercoagulabilityfactor V hypercoagulability In this disorder the Leiden variant of factor V, cannot be inactivated by activated protein C. In this disorder the Leiden variant of factor V, cannot be inactivated by activated protein C.factor Vfactor V

42. Pathophysiology In the normal person, factor V functions as a cofactor to allow factor X to activate an enzyme called thrombin. Thrombin in turn cleaves fibrinogen to fibrin, which polymerizes to form the dense meshwork that makes up the majority of a clot. In the normal person, factor V functions as a cofactor to allow factor X to activate an enzyme called thrombin. Thrombin in turn cleaves fibrinogen to fibrin, which polymerizes to form the dense meshwork that makes up the majority of a clot. cofactorfactor Xenzymethrombin fibrinogenfibrinclot cofactorfactor Xenzymethrombin fibrinogenfibrinclot Activated protein C (aPC) is a natural anticoagulant that acts to limit the extent of clotting by cleaving and degrading factor V. Activated protein C (aPC) is a natural anticoagulant that acts to limit the extent of clotting by cleaving and degrading factor V.protein C anticoagulantprotein C anticoagulant Such mutation makes factor V less suseptable to cleavage by APC. Such mutation makes factor V less suseptable to cleavage by APC.

43. Pathophysiology Factor V Leiden is a condition in which the coagulation factor cannot be destroyed by aPC. Factor V Leiden is a condition in which the coagulation factor cannot be destroyed by aPC. When factor V remains active, it facilitates overproduction of thrombin leading to excess fibrin generation and excess clotting. When factor V remains active, it facilitates overproduction of thrombin leading to excess fibrin generation and excess clotting. The excessive clotting that occurs in this disorder is almost always restricted to the veins, where the clotting may cause a deep vein thrombosis (DVT). The excessive clotting that occurs in this disorder is almost always restricted to the veins, where the clotting may cause a deep vein thrombosis (DVT).veinsdeep vein thrombosisveinsdeep vein thrombosis It is also known as protein C-resistance (APC-R) It is also known as protein C-resistance (APC-R)

44. This will lead to many problems, such as: Women with the disorder have an increased risk of miscarriage stillbirth, as well as preeclampsia due to clotting in the placenta, umbilical cord, or the fetus. Women with the disorder have an increased risk of miscarriage stillbirth, as well as preeclampsia due to clotting in the placenta, umbilical cord, or the fetus.preeclampsia Patients with vein thrombosis have this condition. Patients with vein thrombosis have this condition. Patients with vein thrombosis Patients with vein thrombosis

45. Diagnosis Suspicion of factor V Leiden being the cause for any thrombotic event should be considered in any white patient below the age of 45, or in any person with a family history of venous thrombosis. Suspicion of factor V Leiden being the cause for any thrombotic event should be considered in any white patient below the age of 45, or in any person with a family history of venous thrombosis. This disease can be diagnosed by watching the aPTT as activated protein C is added. With a normal patient, adding APC increases the aPTT. In patients with factor V Leiden, adding APC to plasma of Factor V leiden will fail to prolong APTT. This disease can be diagnosed by watching the aPTT as activated protein C is added. With a normal patient, adding APC increases the aPTT. In patients with factor V Leiden, adding APC to plasma of Factor V leiden will fail to prolong APTT.aPTT There is also a simple genetic test that can be done for this disorder, and will give a quick diagnosis. There is also a simple genetic test that can be done for this disorder, and will give a quick diagnosis.

47. Antithrombin (AT) deficiency Antithrombin (AT) is a small protein molecule that inactivates several enzymes of the coagulation system. Antithrombin (AT) is a small protein molecule that inactivates several enzymes of the coagulation system.coagulation

48. Function The physiological target of antithrombin are those of the contact activation pathway (formerly known as the intrinsic pathway), namely the activated forms of Factor X (Xa), Factor IX (IXa), Factor XI (XIa), Factor XII (XIIa) and Factor II (thrombin) (IIa) and also the activated form of Factor VII (VIIa) from the tissue factor pathway (formerly known as the extrinsic pathway) The physiological target of antithrombin are those of the contact activation pathway (formerly known as the intrinsic pathway), namely the activated forms of Factor X (Xa), Factor IX (IXa), Factor XI (XIa), Factor XII (XIIa) and Factor II (thrombin) (IIa) and also the activated form of Factor VII (VIIa) from the tissue factor pathway (formerly known as the extrinsic pathway)contact activation pathwayFactor XFactor IXFactor XI Factor XIIFactor IIFactor VIItissue factor pathwaycontact activation pathwayFactor XFactor IXFactor XI Factor XIIFactor IIFactor VIItissue factor pathway

49. Pathology: Inherited. Inherited. Causes recurrent venous thrombosis, occasionally causes arterial thrombosis. Causes recurrent venous thrombosis, occasionally causes arterial thrombosis. AT concentrate are available and are used to prevent thrombosis during surgery or childbirth. AT concentrate are available and are used to prevent thrombosis during surgery or childbirth. The disease leads to increased prothrombin levels. The disease leads to increased prothrombin levels.

50. Hyperhomocysteinemia Definition: An amino acid produced by the body, derived from the digestion of protein-rich foods. Definition: An amino acid produced by the body, derived from the digestion of protein-rich foods. Homocystein is derived from dietary methionin and is metabolized either by the remethylation or the trans- sulphuration pathways. Homocystein is derived from dietary methionin and is metabolized either by the remethylation or the trans- sulphuration pathways. Supplementation with folic acid or B12 reduces the concentration of homocysteine in the bloodstream. Supplementation with folic acid or B12 reduces the concentration of homocysteine in the bloodstream. Normal fasting homocysteine plasma levels are between 5,0 and 15,9 mmol/l. Normal fasting homocysteine plasma levels are between 5,0 and 15,9 mmol/l. Hyperhomocysteinemia is a medical condition characterized by an abnormally large level of homocysteine in the blood. Hyperhomocysteinemia is a medical condition characterized by an abnormally large level of homocysteine in the blood. homocysteineblood homocysteineblood

51. Classical Hyperhomocysteinemia: Is a rare autosomal recessive disorder but it can also be acquired Is a rare autosomal recessive disorder but it can also be acquired Vascular disease and thrombosis are major features of the disease. Vascular disease and thrombosis are major features of the disease. Higher levels are associated with increased risk of both venous and arterial thrombosis. Higher levels are associated with increased risk of both venous and arterial thrombosis.

52. Acquired risk factors: Decreased folate levels. Decreased folate levels. Decreased vitamin B12 levels. Decreased vitamin B12 levels. Decreased vitamin B6 levels. Decreased vitamin B6 levels. Drugs (e.g. cyclosporine). Drugs (e.g. cyclosporine). Renal damage. Renal damage. Smoking. Smoking. The risk is increased with age and it is higher in men and menopausal women. The risk is increased with age and it is higher in men and menopausal women.