- Hemorrhage: constitutes the most frequent and important adverse reaction of heparin treatment. Hemorrhage risk increases when there is a prior medical history of ulcers or brain hemorrhage. The risk is also greater if heparin is administered intravenously in large dosages and in a intermittent way. This is why intravenously administered heparin is typically done by driven pump for continous perfusion.
- Because of the risk of hemorrhage, it is necessary to maintain a strict coagulation control. The monitoring of the administration of therapeutical doses of unfractioned heparin is usually done through aPPT or activated Partial Thromboplastine Time. A prolongation of aPPT from 1.5 to 2.5 in relation to the reference value (equivalent to 0.3-0.7U anti-Xa/mL) is considered adequate, although this may vary depending on the reagents used by each laboratory. Control must be carried out within six hours of the first administration; the heparin dosage is further adjusted depending on the results.
If the treatment with unfractionated heparin causes a hemorrhage, the infusion must be stopped and local measures must be applied, as the anticoagulant effect will disappear in 2 or 3 hours.
If the hemorrhage is critical or life threatening, one can resort to protamine sulfate to neutralize it (1 mg of protamine sulfate will be enough to neutralize 100 U of heparin). One must administer a dosage of protamine sulfate equivalent to the amount of heparin perfused during the last two hours, and it must be taken into account that the protamine sulfate only partially neutralizes the activity of the low-molecular heparin. Fresh Frozen Plasma is not effective to reverse the effect of the heparin.
- Heparin-induced thrombocytopenia: there can be a moderate reduction in the number of platelets; which may happen during the first few days of heparin treatment. This kind of thrombocytopenia can remain above 100x109/L, and does not have clinical manifestations. Otherwise, there is another, less frequent, type of thrombocytopenia which appears within 5 to 14 days from the beginning of the treatment. Its origin lay in the formation of antibodies against the heparin-platelet factor 4 complex. This kind of thrombocytopenia is much more acute, and presents the following symptoms: hemorrhage and arterial or venous thrombosis.
- Allergic reactions: manifests itself in the form of fever, cutaneous reactions or digestion pain.
- Osteoporosis: the loss of bone mineral density may appear after a very lengthy treatment with heparin. .