HIT can be benign, or life threatening
HIT—defined by a decrease in platelet count to less than 150,000 (or a 50% drop from baseline) after initiation of heparin therapy—may or may not be benign. HIT type I (previously called heparin-associated thrombocytopenia), which affects approximately 10% of patients treated with heparin, is transient, asymptomatic, and not associated with an increased risk of thrombosis. Type I typically occurs within the first 2 days of heparin therapy.15
HIT type II is an immune-mediated response that does increase the risk of thrombosis. Patients usually develop type II 5 to 12 days after initiation of heparin, but in rare instances onset is delayed, occurring up to 40 days after heparin therapy. Approximately 5% of patients on heparin develop HIT type II, and the risk increases with frequent heparin use. Unlike other states of thrombocytopenia, HIT rarely causes bleeding. However, patients with HIT type II are at risk for a paradoxical thrombotic syndrome that may become life threatening.13,15
To diagnose HIT, an enzyme-linked immunosorbent assay or other specific blood tests must be used to confirm the presence of circulating antibodies.13 The diagnosis is based on the following criteria: (1) thrombocytopenia, (2) exclusion of other possible causes of thrombocytopenia, and (3) resolution of thrombocytopenia after discontinuation of heparin.13,15
When HIT is suspected, all heparin-containing products must be discontinued immediately and alternative anticoagulant therapy (typically, with danaparoid, lepirudin, or argatroban) should be initiated to reduce the risk of thrombosis. Warfarin alone should not be used for the treatment of HIT because of its association with worsening thrombosis and venous limb gangrene.13 However, warfarin should be initiated while the patient is receiving danaparoid or a thrombin-specific inhibitor—with at least 5 days of overlapping therapy recommended. Duration of therapy has not been well defined, but an overall course of at least 2 to 3 months is recommended to reduce the risk of recurrent thrombosis.13,15
Pregnancy raises risk, but limits Tx options
By altering the body’s normal physiologic state in a way that may lead to hypercoagulability, pregnancy increases the risk of VTE 6-fold.16 The risk continues throughout pregnancy and peaks during puerperium, the 6-week period after delivery. Cesarean delivery, prolonged immobility, and obesity elevate the risk.13,16
Treatment options for acute thrombotic events during pregnancy are limited because warfarin is contraindicated. Current ACCP guidelines recommend substituting UFH or LMWH for oral anticoagulant therapy when treatment for an acute thrombotic event is required.10 While no pharmacologic prophylaxis is currently recommended for pregnant patients with thrombophilias but no history of thrombotic events,10,17 there are cases when it may be necessary. Patients with an AT deficiency, for example, may require prenatal and postpartum prophylaxis,10 and patients who deliver by cesarean and have 1 or more additional risk factors should receive prophylaxis for the duration of their hospitalization. Women with multiple risk factors, in addition to pregnancy and cesarean section, should receive pharmacologic prophylaxis for up to 4 to 6 weeks postpartum.
Choices for postpartum anticoagulation for the treatment of an acute thrombotic event should be based on guidelines developed for nonpregnant patients, with this caveat: For women who are breastfeeding, safety during lactation must be considered. Neither UFH nor warfarin enters breast milk, so both are safe for such patients.18 LMWH, although smaller in molecular weight than UFH, is considered moderately safe during breastfeeding, as well.18
Prophylaxis is vital for trauma patients
Trauma and major injuries increase the risk of thrombosis by approximately 50%. Patients who are hospitalized after a major trauma are at high risk for the development of a VTE. At the greatest risk are those with spinal cord injuries (62%), pelvic fractures (61%), and leg fractures (80%).16 Current ACCP guidelines recommend the use of LMWH as soon as it is safe for trauma patients, and continuing it until discharge in patients with no apparent contraindication. If a patient has an active bleed or other contraindication, mechanical thromboprophylaxis is indicated until the bleeding risk decreases.15
Estrogens increase platelet aggregation
Estrogens are considered a risk factor because of their effect on both natural anticoagulants and clotting factors. A reduction in AT activity and increasing concentrations of clotting factors VII, X, and XII result from the use of estrogens. Estrogen is also thought to be responsible for the increase in platelet count and aggregation associated with the use of combination OCs.19 In fact, OC use is associated with about a 3-fold overall risk of thrombosis, a risk reported to be highest during the first year of use.16 Among hormonal contraceptives, the transdermal formulation has the highest risk.20-22 Hormone replacement therapy taken during menopause confers approximately a 2- to 4-fold increase in risk for VTE, and selective estrogen receptor modulators are associated with a 2-fold risk.16 Physicians should educate patients about the risks associated with these agents and signs and symptoms of thrombosis.