Treatment of clotting disorders

Compound 165 and its derivatives inhibit serine protease enzymes such as TF/factor Vila and Xa (tissue factor) <2004USP0235852>. Benzofurans 166 and 167, which have transposed functional groups, are both TF/factor X inhibitors. Tissue factors are involved in the release of thrombin, so these compounds are applied to the treatment of clotting disorders <2003W003082847, 2005JPP2005120080>. Diarylbenzofuran 168 is used to inhibit bone loss <1996USP5489587>. 

Figure 34-1. Classes of drugs used in the treatment of clotting disorders.

Therapeutic plasma exchange (TPE), or plasmapheresis (PP), is an extracorporeal therapy most frequently used in the treatment of hematologic disorders, and autoimmune neuropathies and vasculitides [37]. This modality occasionally is also employed in the treatment of poisoning. The apparatus involves central venous access and a blood circuit between the patient and a pheresis machine. Cytopheresis by centrifugation or filtration then separates the formed elements of blood from plasma. The cells are returned to the patient while the plasma (with the poison) is discarded. Fluid volume is typically replaced with crystalloid, colloid, or fresh frozen plasma (FFP) if clotting factor repletion is necessary. 

Attention must be paid to severe clotting disorders, cardiac and coronary insufficiency, severe cardiac arrhythmia, serious hypertension, respiratory insufficiency and purulent peritonitis as possible contraindications. The same is true of Bekhterev s disease and cerebral insufficiency (depending on the respective severity). Despite a wide range of indications, the list of contraindications (with the exception of hepatogenic clotting disorders) only covers severe extrahepatic diseases. In these cases, it is the treatment of the serious condition which is of paramount importance and not the diagnostic clarification of abdominal or hepatobiliary diseases. (228, 244, 254, 266, 275) (s. tab. 7.13)... 

Favorable results of exchange transfusion in a variety of diseases in adults, for example sickle cell disease, severe clotting disorders, hepatic failure, and acute hemolytic transfusion reactions, have been published (1). Today, however, machine apheresis procedures are more effective and safer for patients requiring exchange of cellular elements or plasma. Exchange transfusion is the most effective therapeutic procedure in the treatment of hemolytic disease of the newborn. Bilirubin removal prevents damage to the central nervous system caused by hyperbilirubinemia. In addition, sensitized erythrocytes are replaced by normally surviving cells and anemia is corrected. 

Argatroban has been approved in the USA and Canada for the prophylaxis and treatment of thrombosis in patients with heparin-induced thrombocytopenia, and in Japan and Korea for various thrombotic disorders. Its effects can be monitored using the activated partial thromboplastin time for low doses and the activated clotting time for high doses. Its pharmacology, clinical pharmacology, and uses have been reviewed (7-14). 

HEART AND BLOOD VESSEL DISORDERS. Many of the ideas about heart disease which have been popularized by the mass media are limited to the dramatic aspects of blood clots, cardiac arrest, clogging of the blood vessels with plaques, excruciating pain, and sudden death. However, these tispects represent only the later stages of the disease. Detection and treatment of the early stages may forestall the later stages for a long time. Hence, it is worthwhile to consider the various aspects of the cardiovascular disorders that follow. 

Systemic clotting dysfunction is a potential contributory factor in more than 30% of cirrhotic patients with gastrointestinal bleeding. The seriousness of the haemorrhage depends to a great extent on the severity of the haemostatic disorder. Localized treatment must therefore be supplemented by additional corrective therapeutic measures, especially since a deterioration of the haemostatic potential in a haemorrhagic patient may occur rapidly and with serious consequences. The prep-... 

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