The Perioperative Management of Heparin Induced Thrombocytopenia Chaitan K. Narsule, M.D. March 5, 2008
Overview Case Presentation Incidence of HIT Pathophysiology Clinical Presentation Laboratory Diagnosis Treatment Prevention Perioperative Considerations
Case Presentation
Case Presentation 48 year old man with extensive hx of rheumatoid arthritis Had contracture of left foot Underwent orthopaedic procedures* for left foot contracture Two weeks later, presented to ED with cold, pulseless left leg *arthrodesis, Achilles tendon lengthening, and talar exostectomy
Laboratory Data 131 103 18 13.1 135 7.8 30 3.2 19 1.1 PT = 13.9 INR = 1.3 aptt = 46.7 Lactic acid = 1.6.
Case Presentation HIT was presumed. Argatroban was started. Patient underwent iliofemoral thrombectomy and left leg fasciotomies
Case Presentation Over one week later, developed severe abdominal pain, distension, and fever. Had an elevated WBC, platelet count of 12k, and was still on Argatroban. CT scan of the abdomen
What do you do now? or.
Incidence of HIT
At-Risk Populations for HIT Post-op patients Orthopaedic patients Cardiac/Vascular/General surgical patients Obstetric patients Medical patients
Arepally et al. NEJM 2006. 355;8:809-817
Gender Imbalance and HIT Warkentin et al. Blood 2006;108:2937-2941
Pathophysiology
Ahmed et al. Postgrad Med J 2007;83:575-582
Pathophysiology Abs recognize heparin induced conformational change in PF4 molecule Keeling et al. Br J Haem 2006;133:259-269.
Type I Type I vs. Type II HIT Asymptomatic, mild decrease in platelet count (usually >100 x 10 9 /L) Incidence ~10-20% of all patients on heparin. Non-immunogenic response to heparin. Platelets recover even with continuation of heparin. Menajovsky. Am J Med 2005;118:21s-30s
Clinical Presentation
The Vernacular of HIT Clinical (Isolated) HIT Rapid Onset HIT Heparin Induced Thrombocytopenia with Thrombosis (HITT)
Clinical HIT Antibody formation after heparin administration is accompanied by unexplained platelet fall 50% Fall typically begins 5-10 days after heparin administration Thrombocytopenic levels (i.e. 50% fall or to <150 x 10 9 /L) reached 7 to 14 days after starting heparin Keeling et al. Br Soc Haem 2006;133:259-269
The Temporal Nature of HIT Warkentin et al. NEJM 2001;344:1286-1292
Rapid-Onset HIT 25-30% of patients <4 days post heparin administration associated with previous heparin exposure within past 100 days Keeling et al. Br Soc Haem 2006;133:259-269 Warkentin et al. NEJM 2001;344:1286-1292
HITT HIT can be associated with clinical evidence of thrombosis Incidence ~50% of cases Warkentin et al. Chest 2004;126:311s-337s
HITT Warkentin. Arch Pathol Lab Med 2002;126:1415-1423 Menajovsky. Am J Med 2005;118:21s-30s Warkentin et al. Ann Int Med 1997;127:804-812
Heparin-Induced Thrombocytopenia with Thrombosis: Loyola Experience (1991-94) Nand et al. Am J Hematol 1997;56;12-16
Heparin-Induced Thrombocytopenia with Thrombosis: Loyola Experience (1991-94) 29% HITT rate 9% rate of amputations 16% mortality Nand et al. Am J Hematol 1997;56;12-16
Laboratory Diagnosis
Laboratory Diagnosis Diagnosis of HIT is based on clinical presentation Identifying HIT antibodies is useful to corroborate diagnosis Clinical pretest probability must be established in order to determine the reliability of a positive or negative result
Keeling et al. Br Soc Haem 2006;133:259-269
Warkentin. Arch Pathol Lab Med 2002;126:1415-1423 Menajovsky. Am J Med 2005;118:21s-30s
Serologic vs. Functional Assays Serologic Assays Detect circulating IgG, IgA, and IgM antibodies Have high sensitivity (> 97%) Limited specificity (~74-86%) Can detect PF4-heparin Abs in patients without HIT Can be improved if IgG s are only examined Commercially unavailable Recommended when clinical suspicion of HIT is high or intermediate Arepally et al. NEJM 2006. 355;8:809-817
Serologic vs. Functional Assays Functional Assays Measure platelet activation Detect heparin-dependent antibodies capable of binding and activating Fc receptors on platelets Sensitivity > 90% at experienced labs Specificity ~ 77-100% Labor intensive Not widely available Recommended to confirm HIT in patients with intermediate probability with indeterminate serologic testing Arepally et al. NEJM 2006. 355;8:809-817
Warkentin. Arch Pathol Lab Med 2002;126:1415-1423
Treatment
De Nisio et al.. NEJM 2005;353:1028-1040
Fondaparinux Renal Approved for DVT prophylaxis, not HIT treatment Arepally et al. NEJM 2006. 355;8:809-817
DTI-VKA Overlap Warkentin et al. Chest 2004;126:311s-337s
Warfarin for HIT Can cause venous limb gangrene when given as monotherapy for HIT Due to associated hypercoagulability and depletion of Protein C Administered when platelet count has recovered ( 100 x 10 9 /L) during HIT treatment Warkentin et al. Ann Int Med 1997; 127:804-812 & Chest 2004;126:311s-337s
LMWH for Treating HIT Retrospective cohort study of 89 patients Following dx of HIT, patients received: LMWH (n = 36) Warfarin (n = 27) Danaparoid (n = 9) Nothing (n = 17) Ranze et al. Ann Hematol 2000;79:P198
LMWH for Treating HIT New thrombosis: 47.2% of patients receiving LMWH 33.3% of patients receiving warfarin 23.5% of patients receiving no anticoagulation 0% of patients receiving danaparoid 36.1% of patients treated with LMWH had recovery of platelets, compared with other approaches (~81% overall, p < 0.001) Ranze et al. Ann Hematol 2000;79:P198
Prevention
Not proven in other non-orthopaedic surgery settings Warkentin et al. Arch Int Med 2003;163:2518-2524, NEJM 1995;332:1330-5, & Chest 2004;126:311s-337s UFH vs. LMWH in Preventing HIT LMWH is associated with lower incidence of HIT than UFH in postop orthopaedic patients
Martel et al. Blood 2005;106:2710-2715)
Perioperative Considerations
Platelet Count Recommendations HIT risk > 1% (frequent): Patients receiving post-op antithrombotic prophylaxis with UFH Every-other-day platelet count monitoring between post-op days 4 to 14, or until UFH is stopped HIT risk 0.1 to 1% (infrequent): Medical/obstetric patients receiving prophylactic dose UFH (or LMWH after receiving UFH), post-op patients receiving prophylactic dose LMWH or intravascular catheter UFH flushes Platelet count monitoring every 2 to 3 days from day 4 to 14, or until heparin is stopped Warkentin et al. Chest 2004;126:311s-337s
Platelet Count Recommendations HIT risk < 0.1% (rare): Medical or obstetric patients receiving LMWH or UFH flushes Platelet count monitoring not needed Screening for subclinical HIT antibody seroconversion: Warkentin et al. Chest 2004;126:311s-337s
Prophylactic Platelet Transfusions Contraindicated if no evidence of active bleeding Associated with thrombotic events in anecdotal reports In severe thrombocytopenia, petechiae and mucocutaneous bleeding are not typical features of HIT Warkentin et al. Chest 2004;126:311s-337s
Cardiac or Vascular Surgery in Patients with Previous HIT No anamnestic immune response in HIT HIT antibodies are transient Warkentin et al. NEJM 2001;344:1286-1292
Cardiac or Vascular Surgery in Patients with Previous HIT After confirmed seronegativity following HIT, antibodies do not always regenerate following repeat heparin challenge Regenerated antibodies do not occur sooner, or at stronger levels Warkentin et al. NEJM 2001;344:1286-1292
Cardiac or Vascular Surgery in Patients with Previous HIT For HIT antibody negative patients: UFH is recommended for surgery Nonheparin anticoagulants should be used for preoperatively and postoperatively, if needed For acute or subacute HIT patients: Nonheparin anticoagulants are recommended unless surgery can be delayed until patients are HIT antibody negative Warkentin et al. Chest 2004;126:311s-337s
Warkentin et al. Chest 2004;126:311s-337s
Conclusions
This presentation is available for further review at: www.chaitannarsule.com/surgery
The Perioperative Management of Heparin Induced Thrombocytopenia Chaitan K. Narsule, M.D. March 5, 2008