Haemorrhage anticoagulants

Due to bleeding risk, individuals on anticoagulant therapy or individuals who are vitamin K-deficient should not take vitamin E supplementation without close medical supervision. Absent of that, vitamin E is a well-tolerated relatively non-toxic nutrient. A tolerable upper intake level of 1,000 mg daily of a-tocopherol of any form (equivalent to 1,500 IU of RRR a-tocopherol or 1,100 IU of all-rac-a-tocopherol) would be, according to the Food and Nutrition Board of the Institute of Medicine, the highest dose unlikely to result in haemorrhage in almost all adults. 

Heparin, which has an anticoagulation action, may give rise to heparin-induced thrombocytopenia, which is an immune-mediated condition that usually develops 5-10 days after the administration of the drug. When heparin is used, a platelet count should be measured before treatment and if administration is repeated, platelet counts should be monitored regularly. Signs of thrombocytopenia include a reduction in platelet count. It may present with spontaneous haemorrhage and heparin should be stopped. Factor VIII is used in the treatment and prophylaxis of haemorrhage in patients with haemophilia. 

Coumarins are also synthesized by a variety of plant species. Medically, the most significant coumarins are dicoumarol and its derivative, warfarin. Dicoumarol was initially discovered as the active substance in mouldy sweet clover hay, which could induce haemorrhagic disease in cattle. Dicoumarol and warfarin are now used clinically as anticoagulants, as discussed in Chapter 9. 

The only major side-effect of these oral anticoagulants is prolonged bleeding, thus the dosage levels are chosen with care. Dicoumarol was first isolated from spoiled sweet clover hay, as the agent which promoted haemorrhage disease in cattle. Both dicoumarol and warfarin have also been utilized (at high doses) as rat poisons. 

Therapeutically, vitamin K is used in prophylaxis and treatment of deficiency of clotting factor due to dietary deficiency of vitamin K, chronic antimicrobial therapy, malabsorption syndrome, obstructive jaundice, liver diseases such as cirrhosis and hepatitis, in neonates to prevent or treat haemorrhagic disease of new born to counteract the overdosing of oral anticoagulants... 

Van Cauwenberge H, Jaques LB. Haemorrhagic effect of ACTH with anticoagulants. Can Med Assoc J 1958 79(7) 536 i0. 

Ischaemic and haemorrhagic strokes are identified by CT scan within 24—48 hours of a stroke, not by clinical signs and symptoms. However, seizures, nausea, vomiting and headache may increase the clinical likehood of haemorrhagic stroke. Haemorrhagic strokes must not be treated with any anticoagulants (e.g. aspirin) in the acute phase, whereas this is recommended for patients with ischaemic stroke. 

When these patients are discharged from hospital, prophylactic treatment with an oral anticoagulant is recommended to prevent recurrence of the thrombosis. Warfarin sodium, which antagonizes the effects of vitamin K, is used in prophylaxis and treatment of DVT and pulmonary embolism. It is usual to start with an induction dose of 10 mg daily for two days the dose can then be reduced. Patients need to be monitored as there is a risk of haemorrhage with oral anticoagulant drugs. 

PENTOXIFYLLINE ANTICOAGULANTS-ORAL Case reports of major haemorrhage when pentoxifylline was given with acenocoumarol Uncertain possibly additive effect (pentoxifylline has an antiplatelet action) Monitor INR closely... 

ANTICOAGULANTS-ORAL CRANBERRY JUICE Cases of markedly T anticoagulant effect (including fatal haemorrhage) with regular cranbeny juice ingestion Uncertain possibly due to inhibition of CYP-mediated metabolism of warfarin Patients taking warfarin should avoid cranberry juice... 

ANTICOAGULANTS - ORAL GRAPEFRUIT JUICE t efficacy and t adverse effects of warfarin e.g. t INR, haemorrhage Unclear. Possibly via inhibition of intestinal CYP3A4 Monitor INR more closely. Avoid concomitant use if unstable INR... 

Anticoagulants - a risk of catastrophic haemorrhage from the gastric mucosa. Remember that other drugs, for example antidepressants such as SSRIs and MAOIs, may have an anticoagulant side-effect. 

Drugs given to the mother just prior to labour can cause postnatal effects CNS depressants may persist in and affect the baby for days after birth vasoconstrictors can cause fetal distress by reducing uterine blood supply 3-adrenoceptar blockers may impair fetal response to hypoxia sulphonamides displace bilirubin from plasma protein (risk of kernicterus) anticoagulants can cause haemorrhage. 

Cutaneous reactions, apart from purpura and ecchymoses in those who are excessively anticoagulated, include hypersensitivity, rash and alopecia. Skin necrosis due to a mixture of haemorrhage and thrombosis occurs rarely where induction of warfarin therapy is over-abrupt and/or the patient has a genetically determined or acquired deficiency of the anticoagulant protein C or its cofactor protein S it can be very serious. 

Butler AC, Tail RC. Management of oral anticoagulant-induced intracranial haemorrhage. Blood Rev 1998 12(1) 35 4. 

Dicoumarol, warfarin + p-aminosalicyclic acid Increased anticoagulant serum levels with risk of haemorrhage Displacement from protein Monitor anticoagulant effect, especially with initiation or cessation of therapy... 

Warfarin + mefenamic acid Enhanced anticoagulant blood levels with risk of haemorrhage and enhanced risk of Gl bleeding Displacement from protein Concurrent administration is best avoided. If necessary, coagulation limes should be monitored... 

Gallerani M, Manfredini R, Moratelli S. Non-haemorrhagic adverse reactions of oral anticoagulant therapy. Int J Cardiol 1995 49 1-7. 

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