Protein C deficiency

Coumarin is also widely used for long-term anticoagulation in chronic atrial fibrillation (particularly to avoid cardioembolic strokes), to prevent DVT or PE in patients with chronic hypercoagulability (e.g., congenital AT or protein C deficiency), or to prevent... 

Tests for hypercoagulable states, such as protein C deficiency and antiphospholipid antibody, should be done only when the cause of stroke cannot be determined based on the presence of well-known risk factors for stroke. 

Homozygous protein C deficiency can cause life-threatening thrombotic syndromes immediately after birth. 

Individuals with heterozygous protein C deficiency are seven times more likely to be afflicted with venous thrombosis than normal individuals. A combination of protein C deficiency with a mutation in the factor V gene (factor V Leiden) carries a much greater risk for venous thrombosis than the presence of only one of these conditions (89). 

Reitsma P. H. Protein C deficiency From gene defects to disease. Thromb Haemost 1997 78, 344-50. 

Protein C concentrate (Human) Purpura fuhninans and coumarin-induced skin necrosis in patients with severe congenital protein C deficiency... 

Patients with CHF may exhibit greater than expected PT/INR response to warfarin. Protein C deficiency Known or suspected hereditary, familial, or clinical deficiency in protein C has been associated with necrosis following warfarin therapy. 

Coumarin-induced skin necrosis is a rare complication of oral anticoagulant therapy. Especially patients suffering from a rare and life-threatening blood disorder known as protein C deficiency are at risk. In these cases Protein C Concentrate (human). 

Ceprotin, can be given. Ceprotin is of course also indicated for patients with severe congenital Protein C deficiency for the prevention and treatment of venous thrombosis and purpura fulminans. 

Unlabeled Uses Antithrombin ill deficiency, arterial occlusions, hemophilia A, lichen sclerosus et atrophicus, liposclerosis, necrobiosis lipoidica, osteoporosis, protein C deficiency, rheumatoid arthritis, thrombosis, urticaria... 

Data from the Leiden Thrombophilia Study have been used to construct a case-control study, based on contraceptive users who had experienced a first episode of objectively proven deep vein thrombosis (100). Patients and controls were considered thrombophilic when they had protein C deficiency, protein S deficiency, antithrombin deficiency, factor V Leiden mutation, or a prothrombin 20210 A mutation. Among healthy women, the risk of developing deep vein thrombosis was trebled in the first 6 months and doubled in the first year of contraceptive use. Among women with thrombophilia, the risk of deep vein thrombosis was increased 19-fold during the first 6 months and 11-fold (95% Cl = 2.1, 57) in the first year of use. Venous thrombosis during the first period of oral contraceptive use might actually point to the presence of an inherited clotting defect. 

As low levels of protein C activation peptide are found in healthy individuals, it is suggested that protein C is constantly activated to a small degree (124). Protein C administration has been shown to inhibit both arterial and venous thrombosis in animal models (125). Heterozygous protein C deficiency or activated protein C resistance due to factor V mutation is thought to explain 60% to 70% of the cases of familial thrombophilia (I 16). 

Small, friable and sterile vegetations made of fibrin and platelets can be found on the heart valves of patients with cancer, in the antiphospholipid antibody syndrome systemic lupus erythematosus and possibly in protein C deficiency. Thrombotic emboli from such vegetations can be demonstrated using trans-esophageal echocardiography and are frequently seen in patients with cancer and cerebral ischemia (Dutta et al. 2006b). 

Thrombophilia e.g. antithrombin III deficiency, protein C deficiency, factor V Leiden mutation, protein S deficiency, plasminogen abnormality or deficiency Leukemia/lymphoma Polycythemia... 

Thrombophilias and other causes of hypercoagulability are rare causes of stroke (Matijevic and Wu 2006). Antithrombin III deficiency, protein C deficiency, activated protein C resistance owing to factor V Leiden mutation, protein S deficiency and plasminogen abnormality or deficiency can all cause peripheral and intracranial venous thrombosis. Thrombosis is usually recurrent and there is often a family history. Thrombophilia may cause arterial thrombosis, although the alternative diagnosis of paradoxical embolism should always be considered in patients with these disorders. It should be noted that deficiencies in any one of the factors associated with thrombophilia may be an incidental finding and cannot necessarily be assumed to be the cause of stroke. 

Lupus anticoagulant Myeloproliferative disease (31) Paroxysmal nocturnal haemoglobinuria Polycythaemia vera Protein C deficiency (68)... 

Sugano, S., Suzuki, T., Makino, H., Yanagimoto, S., Nishio, M., On-mura, H., linuma, M., Matuda, T., Shinozawa, Y. Budd-Chiari syndrome attributed to protein C deficiency. Amer. X Gastroenterol. 1996 91 777-779... 

Protein C, another vitamin K-dependent serine protease zymogen in plasma, is a regulatory protein that, when activated, limits the activity of two activated procoagulant co-factors, factors Va and Villa. Heterozygotes for hereditary isolated protein C deficiency tend to develop a thrombotic disease which has been successfully treated with long-term coumarins (2,3). Apparently, the... 

The pathogenesis is still not completely elucidated, but data suggest that transient protein C deficiency may be causative. 

Patients with hereditary protein C deficiency (59,60) or acquired functional protein C deficiency (61) are particularly susceptible to the development of hemorrhagic skin necrosis. However, skin necrosis has also been reported in patients with deficiency of protein S (a co-factor for protein C), in patients at high thrombogenic risk linked to a constitutional antithrombin III deficit, and in patients with antiphosphohpid antibodies associated with systemic lupus eiythematosus (62,63). 

Prevention of recurrence of coumarin necrosis in patients with protein C deficiency, if treatment is necessary, could consist of transient simultaneous infusion of fresh frozen plasma (leading to a constant concentration of protein C) and heparin both before and at the first time of administration of an oral anticoagulant, associated or not with protein C concentrate (65,66). 

Samama M, Horellou MH, Soria J, Conard J, Nicolas G. Successful progressive anticoagulation in a severe protein C deficiency and previous skin necrosis at the initiation of oral anticoagulant treatment. Thromb Haemost 1984 51(l) 132-3. 

Teepe RG, Brockmans AW, Vermeer BJ, Nienhuis AM, Loeliger EA. Recurrent coumarin-induced skin necrosis in a patient with an acquired functional protein C deficiency. Arch Dermatol 1986 122(12) 1408-12. 

Lewandowski K, Zawilska K. Protein C concentrate in the treatment of warfarin-induced skin necrosis in the protein C deficiency. Thromb Haemost 1994 71(3) 395. 

Zauber NP, Stark MW. Successful warfarin anticoagulation despite protein C deficiency and a history of warfarin necrosis. Ann Intern Med I986 I04(5) 659-60. 

A 5-year-old girl with acquired protein C deficiency had a stroke while taking valproate (69). The authors then measured protein C concentrations in 20 children taking valproate monotherapy and 20 children taking other anticonvulsants. There were significantly lower protein C concentrations in those taking valproate. Protein S and antithrombin III were not affected. Despite this, there is no known association between valproate therapy and a risk of thromboembolic disease, and the clinical relevance of this effect on protein C is not clear. 

Gruppo R, Degrauw A, Fogelson H, Glauser T, Balasa V, Gartside P. Protein C deficiency related to valproic acid therapy a possible association with childhood stroke. J Pediatr 2000 137(5) 714-18. 

Indications Congenital protein C deficiency Category Anticoagulant glycoprotein Half-life 5-15 hours... 

Reitsma PH, Bernard F, Doig RG, Gandrfile S, Greengard JS, Ireland H, et al. Protein C deficiency a database of mutations, 1995 update. Thrombo Haemost 1995 73 876-89. 

Protein C Protein C deficiency, purpura fulminans Unknown 3-5 0.06 Liver IPCU, 2PCT PRTC HUMAN... 

Tests for hypercoagulable states (protein C deficiency, antiphospholipid antibody) should be done only when the cause of the stroke cannot be determined based on the presence of well-known risk factors for stroke. Protein C, protein S, and antithrombin III are best measured in the "steady state," not in the acute stage. Antiphospholipid antibodies as measured by anticardiolipin antibodies, /S2-glycoprotein I, and lupus anticoagulant screen are of higher yield than protein C, protein S, and antithrombin III but should be reserved for patients who are young (<50 years), have had multiple venous/arterial thrombotic events, or have livedo reticularis (a skin rash). 

B9. Beriina, R. M., Broekmans, A. W., Van Der Linden, I. K., and Mertens, K., Protein C deficiency in a Dutch fomily with thrombotic disease. Thromb. Haemostasis 48, 1-5... 

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