Special Problems

Patients with lupus inhibitors who require heparin are difficult to monitor since their aPTTs are already prolonged. One option is to use LMW heparin due to its predictable dosing. The other choice is to directly assay for heparin by measuring its ability to inhibit factor Xa. This assay is insensitive to lupus inhibitors. Therapeutic range for standard heparin is 0.35 - 0.7 anti-Xa units. Heparin assays are also valuable in patients where an acute-phase inflammatory process may lead to nonspecific heparin binding to inflammatory proteins, resulting in the aPTT not reflecting he-parin levels. This can be seen in patients on cyclosporin. In pregnant women the acute rise in factor VIII may also lead to a misleading aPTT; thus, one should use heparin levels to guide therapy in those patients—even with prophylactic doses of standard heparin.

The hypercoagulable state associated with malignancy (especially adenocarcino-mas) may be refractory to warfarin therapy. Long-term LMW heparin is a useful alternative in these patients. Patients should have LMW heparin levels checked weekly until the dose is stable.

Pregnant women with prothrombotic states pose a special problem. Pregnancy adds to the thrombotic risk but is an absolute contraindication to warfarin therapy. The use of heparin was once also feared, but recent re-analysis of the data shows that heparin can be safely used in pregnancy. There is abundant experience with LMW heparin; it is safe and effective in pregnant women for both prophylaxis and therapy. LMW heparin does not cross the placenta and is associated with less osteoporosis than standard heparin. For therapy one should follow LMW heparin levels every 4 weeks. Experience shows that levels are more stable than with standard heparin as the pregnancy progresses.

Since pregnancy is a hypercoagulable state, a patient with additional risk factors for thrombosis should receive prophylaxis. Prophylactic doses of LMW heparin are either enoxaparin at 40 mg/day or dalteparin 5000 units q12 hours. Again, the current recommended approach is to use LMW heparin. To use standard heparin, start with 5-7,500 units of heparin q12 hours and adjust the dose to keep the heparin assay at 0.1-0.2 anti-Xa units. The plasma protein changes which occur with pregnancy render the aPTT inadequate even for monitoring prophylactic doses of heparin. After delivery the patient is on warfarin for six weeks. Warfarin is excreted in the breast milk in an inactive form and is considered safe for breast feeding.

Young pregnant women with mechanical heart valves present difficult problems. Thrombosis with both standard heparin and LMWH valve has been reported. However, the majority of the cases of valve thrombosis have been in patients who were, for unknown reasons, treated with prophylactic and not therapeutic doses of hep-arin. At this time the best approach to treatment is unknown. Options include using standard heparin via continuous infusion pump using heparin levels to monitor therapy, LMWH at doses guided by levels, or use of heparin early, switching to warfarin mid-pregnancy, and then switching back to heparin at 36 weeks.

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