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2032 Part XII: Hemostasis and Thrombosis Chapter 118: Heparin-induced Thrombocytopenia 2033

the appropriate INR target should be followed, because both arga- In light of its documented efficacy and safety in large coronary
124
troban and warfarin increase the INR. This target will vary according angiography trials, bivalirudin is recommended over heparin in patients
to the sensitivity of the prothrombin time reagent to argatroban used in with a history of HIT who require percutaneous vascular procedures,
each institution. irrespective of the results of HIT laboratory testing. 95
DURATION OF ANTICOAGULATION HEMODIALYSIS
Patients with HIT-associated thromboembolism are typically treated Although approximately 10 percent of patients on chronic hemodialy-
with therapeutic anticoagulation for 3 to 6 months. The optimal dura- sis develop circulating anti-PF4–heparin antibodies, the incidence of
131
tion of anticoagulation in patients with HIT without thrombosis (i.e., HIT in this population is less than 1 percent. Ongoing heparin expo-
132
isolated HIT) is unknown. In a historical series of untreated patients sure during dialysis in patients with a history of HIT is contraindicated.
with isolated HIT, the cumulative incidence of thromboembolism at 30 Alternative strategies including regional citrate, saline flushing, danap-
days was 53 percent. Most events occurred within 10 days of heparin aroid, argatroban, and vitamin K antagonists use have been reported. 95
57
cessation, corresponding to the platelet recovery phase. It is therefore
generally accepted that anticoagulation be continued in patients with
isolated HIT until platelet count recovery. Some authorities recommend PREGNANCY
longer courses (e.g., 4 weeks). 122 HIT is rare (<0.1 percent) in pregnant women exposed to heparin. 11,12
When it does occur, initiation of a nonheparin anticoagulant is war-
PLATELET TRANSFUSION ranted. The largest published experience is with danaparoid. A ret-

There is a long-held concern that platelet transfusion may precipitate rospective cohort of 30 women with acute HIT received danaparoid
133
during pregnancy. Five patients developed thrombosis and three
thrombosis in HIT by “adding fuel to the fire.” Two case series chal- developed major bleeding. Danaparoid does not cross the placenta
lenge this dogma. Collectively, these series included 41 patients with and there was no measurable anti-Xa activity in the cord blood of six
suspected HIT who underwent platelet transfusion. None developed neonates who were tested after delivery. If danaparoid is unavailable,
thrombosis during extended followup. 125,126 Nevertheless, because HIT fondaparinux may be considered though evidence supporting its use
is characteristically prothrombotic rather than prohemorrhagic, pro- in pregnant women with HIT is limited to case reports 134,135 and partial
phylactic platelet transfusion is rarely indicated. Transfusion may be transplacental passage has been demonstrated. 136
considered in the setting of clinically significant bleeding, high bleeding
risk, or diagnostic uncertainty.
REFERENCES
HEPARIN REEXPOSURE IN PATIENTS 1. Kelton JG, Warkentin TE: Heparin-induced thrombocytopenia: A historical perspec-
WITH A HISTORY OF HEPARIN-INDUCED tive. Blood 112;2607, 2008.
THROMBOCYTOPENIA 2. Chong BH, Berndt MC: Heparin-induced thrombocytopenia. Blut 58:53, 1989.
3. Fratantoni JC, Pollet R, Gralnick HR: Heparin-induced thrombocytopenia: Confirma-
tion of diagnosis with in vitro methods. Blood 45:395, 1975.
In general, heparin reexposure should be avoided in patients with a his- 4. Cines DB, Tomaski A, Tannenbaum S: Immune endothelial-cell injury in heparin-
tory of HIT because of the risk of reoccurrence. An exception to this associated thrombocytopenia. N Engl J Med 316:581, 1987.
127
rule is the use of intraoperative heparin in patients with a history of HIT 5. Kelton JG, Sheridan D, Santos A, et al: Heparin-induced thrombocytopenia: Labora-
who are undergoing cardiovascular surgery. The HIT immune response tory studies. Blood 72:925, 1988.
wanes over time. Functional assays become negative at a median of 6. Amiral J, Bridey F, Dreyfus M, et al: Platelet factor 4 complexed to heparin is the target
for antibodies generated in heparin-induced thrombocytopenia. Thromb Haemost
50 days after heparin cessation, whereas anti-PF4–heparin antibody 68:95, 1992.
titers decline more slowly and are no longer detectable in 60 percent 7. Warkentin TE, Sheppard JA, Sigouin CS, et al: Gender imbalance and risk factor inter-
actions in heparin-induced thrombocytopenia. Blood 108:2937, 2006.
of patients by day 100. HIT laboratory testing can be used to deter- 8. Warkentin TE, Shepard JA, Horsewood P, et al: Impact of the patient population on the
23
mine the safety of heparin reexposure during cardiovascular surgery. risk for heparin-induced thrombocytopenia. Blood 96:1703, 2000.
Patients with a negative immunologic and functional assay may safely 9. Pouplard C, May MA, Regina S, et al: Changes in platelet count after cardiac surgery
receive UFH during surgery. This was first demonstrated in 10 patients can effectively predict the development of pathogenic heparin-dependent antibodies.
Br J Haematol 128:837, 2005.
with a history of HIT undergoing cardiac surgery, none of whom devel- 10. Selleng S, Malowsky B, Strobel U, et al: Early-onset and persisting thrombocytopenia in
oped clinical reoccurrence. In a newer report, 11 of 17 such patients post-cardiac surgery patients is rarely due to heparin-induced thrombocytopenia, even
128
developed recrudescence of anti-PF4–heparin antibodies, but only one when antibody tests are positive. J Thromb Haemost 8:30, 2010.
developed HIT. Heparin should be strictly avoided in patients with 11. Sanson BJ, Lensing AW, Prins MH, et al: Safety of low-molecular-weight heparin in
129
pregnancy: As systematic review. Thromb Haemost 81:668, 1999.
a positive functional assay. If possible, surgery should be delayed in 12. Fausett MB, Vogtlander M, Lee RM, et al: Heparin-induced thrombocytopenia is rare
these individuals until functional and immunologic assays become neg- in pregnancy. Am J Obstet Gynecol 185:148, 2001.
ative. If surgery cannot be delayed, a nonheparin anticoagulant (e.g., 13. Avila ML, Shah V, Brandão LR: Systematic review on heparin-induced thrombocytope-
nia in children: A call to action. J Thromb Haemost 11:660, 2013.
bivalirudin) should be used. Appropriate intraoperative anticoag- 14. Lubenow N, Hinz P, Thomaschewski S, et al: The severity of trauma determines the
101
ulation of patients with a functional assay that has become negative, immune response to PF4/heparin and the frequency of heparin-induced thrombocy-
but an immunologic assay that remains positive is uncertain. The 2012 topenia. Blood 115:1797, 2010.
American College of Chest Physicians Guidelines recommend a non- 15. Martel N, Lee J, Wells PS: Risk for heparin-induced thrombocytopenia with unfrac-
tionated and low-molecular-weight heparin thromboprophylaxis: A meta-analysis.
heparin anticoagulant in this setting. However, intraoperative heparin Blood 106:2710, 2005.
95
was used uneventfully in three such patients undergoing urgent heart 16. Morris TA, Castrejon S, Devendra G, Gamst AC: No difference in risk for thrombocy-
transplantation. When heparin is administered to patients with HIT, topenia during treatment of pulmonary embolism and deep venous thrombosis with
130
either low-molecular-weight heparin or unfractionated heparin: A metaanalysis. Chest
it should be limited to the intraoperative setting. Pre- and postopera- 132:1131, 2007.
tive exposure should be scrupulously avoided, though patients with a 17. Pohl C, Kredteck A, Bastians B, et al: Heparin-induced thrombocytopenia in neuro-
logic patients treated with low-molecular-weight heparin. Neurology 64:1285, 2005.
history of HIT who are (inadvertently) reexposed to longer courses of 18. Warkentin TE: Fondaparinux: Does it cause HIT? Can it treat HIT? Expert Rev Hematol
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