A Great Clinical Paradox. Narendranath Epperla MD Sowjanya Bapani MD Steven Yale MD, FACP

Transcription

1 A Great Clinical Paradox Narendranath Epperla MD Sowjanya Bapani MD Steven Yale MD, FACP

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3 Initial Presentation 61 y/o Vietnam veteran with a past H/O hypertension, back pain and depression on Lisinopril, Sertraline, Diazepam and Oxycontin was taken to the outside hospital for suicide attempt with polysubstance drug overdose with opiates and benzodiazepines. He was emergently intubated for unresponsiveness in the emergency room. Evidence of aspiration at the time of intubation. Placed on Piperacillin-Tazobactam (Zosyn) 4.5 g intravenous q8 hrs. for aspiration pneumonia.

4 Why was the patient transferred? Intubated for 7 days when he received Low Molecular weight Heparin (LMWH) for DVT prophylaxis and intravenous (IV) pantoprazole for GI prophylaxis. Multiple episodes of temperature spikes after extubation despite being on Zosyn. CT scan of chest was done which showed right lower lobe infiltrate. Vancomycin was added (1g intravenous q12 hrs.) Transferred to our facility for further care.

5 Hospital Course Continued on broad spectrum Antibiotics. Bronchoscopy with bronchioalveolar Lavage was performed which grew Klebsiella and antibiotics were deescalated based on the culture and sensitivity reports to Ceftriaxone 1g intravenous q12 hrs. He was placed on subcutaneous Unfractionated Heparin (UFH) 5000 IU, three times daily for DVT prophylaxis and oral Omeprazole for GI prophylaxis. Transferred to inpatient psychiatric unit a week after admission for subsequent care.

6 Short stay in the Psychiatric Unit At the time of hospital transfer to the inpatient psychiatric unit his platelet count was 672,000u/L (normal 150,000-45,000u/L). He was continued on antibiotics however prophylactic UFH was discontinued. Four days into the psychiatric unit (hospital day 11) he had chest pain and was transferred back to the hospital.

7 Timely Intervention!! EKG revealed an inferior wall ST elevation myocardial infarction. He was taken to the cardiac catheterization lab and had bare metal stent placed to the completely occluded right coronary artery. Post-catheterization he was placed on ASA, clopidogrel, eptifibatide and prophylactic heparin and was transferred to CCU. His platelet count was 322,000u/L on day 12.

8 Platelet count PLATELET TREND Cardiac Catheterization PLATELET TREND

9 What now? On day 13, he experienced right lower extremity pain and swelling with duplex ultrasonography showing thrombus extending through the deep venous system. His platelet count was 158,000u/L (still within normal limits and was not flagged) He was placed on UFH drip (heparin bolus of 750 units followed by initial rate at 15 mg/kg/hr).

10 Platelet count PLATELET TREND Cardiac Catheterization PLATELET TREND DVT Heparin drip

11 The Activity is still on Two days later after initiation of the UFH drip (Day 15) he became hypoxic and hypotensive requiring intubation for hypoxic respiratory failure and pressor support for hypotension with a platelet count of 46,000u/L. CT pulmonary angiogram revealed massive central pulmonary emboli. The patient underwent thrombolysis with alteplase (100mg) with subsequent improvement in his oxygenation and blood pressure.

12 Platelet count PLATELET TREND Cath PLATELET TREND DVT - Heparin bolus 100 PE - Argatroban

13 And the Diagnosis The presence of thrombocytopenia and venous thrombosis raised concern for Heparin induced thrombocytopenia (HIT). Heparin was discontinued, Platelet factor 4 (PF4) and Serotonin release assay (SRA) were sent and he was started on Argatroban. PF4 came back strongly positive (OD of 2.47) and the diagnosis of HIT was confirmed. SRA was positive as well ( 69% release on 0.1 IU/mL UFH and 0% release on 100 IU/mL)

14 Serotonin Release Assay

15 Twist to the Tale He decompensated overnight despite being on argatroban with worsening hemodynamic instability (increased pressor support and low po2 despite 100% FiO2) Emergently taken to the cardiac catheterization lab when he was found to have an occluded RCA stent with severe right ventricular failure. Aspiration thrombectomy was performed and Intra-aortic balloon pump (IABP) and Right ventricular assist device (RVAD) were placed.

16 Platelet count PLATELET TREND Cath PLATELET TREND 300 In-stent thrombosis DVT - Heparin bolus PE - Argatroban Platelet nadir

17 All s Well That Ends Well Platelet count checked next day morning reached the nadir at 9000u/L. The argatroban was continued and his platelet count gradually improved. Eventually IABP and RVAD were taken out and he was weaned off the pressor support and mechanical ventilation. On hospital day 24 his platelet count improved to 198. Argatroban Warfarin bridging and transition to warfarin and discharge to home.

18 Platelet count PLATELET TREND Cath PLATELET TREND 300 In-stent thrombosis DVT - Heparin bolus PE - Argatroban Platelet nadir

19 Discussion

20 HIT A Clinico-Pathologic Syndrome Clinical Thrombocytopenia Thrombosis venous arterial necrotizing skin lesions anaphylactoid reactions DIC Timing other causes less likely Pathologic Heparin-dependent platelet activating IgG Antigen (immuno) assay: PF4 dependent EIA Activation assay: - SRA - Heparin induced platelet activation assay (HIPA)

21 Proposed Explanation for the Presence of Both Thrombocytopenia and Thrombosis in Heparin-Sensitive Patients Who Are Treated with Heparin. Aster RH. N Engl J Med 1995;332:

22 Three Presentations of HIT

23 Treatment of HIT Once HIT is suspected all the heparin products must be discontinued (including LMWH and heparin administered as flushes ). An alternative non-heparin anticoagulant should be started, generally in therapeutic doses (Eg, danaparoid [not available in the United States], lepirudin, or argatroban). Warfarin should not be given during the acute phase of HIT and if warfarin has already been started when HIT is diagnosed, vitamin K (eg, 10 mg over 30 minutes by intravenous injection) should be administered.

24 Treatment Paradoxes of HIT Coumarins (e.g. warfarin) increase risk of microvascular thrombosis in acute HIT (venous limb gangrene; skin necrosis) LMWH is contraindicated to treat HIT despite its lower frequency of causing HIT. Prophylactic platelet transfusions are relatively contraindicated in HIT. High risk of thrombosis persists even after heparin is stopped.

25 Conclusions This case illustrates the fact that despite a normal platelet count, a >50% platelet count drop should raise a red flag for HIT in the right clinical context. The reduced risk for HIT with LMWH (or fondaparinux) prophylaxis, compared with UFH, suggests that preferring these former agents could reduce the risk for HIT.

26 References Warkentin TE. Heparin-induced thrombocytopenia: pathogenesis and management. Br J Haematol 2003;121(4): Arepally GM, Ortel TL. Clinical practice. Heparin-induced thrombocytopenia.nengl J Med 2006; 355(8): Warkentin TE. Management of heparin-induced thrombocytopenia: a critical comparison of lepirudin and argatroban. Thromb Res 2003;110(2 3): Warkentin TE, Kelton JG. Delayed-onset heparin-induced thrombocytopenia and thrombosis. Ann Intern Med 2001;135(7): Rauova L, Zhai L, Kowalska MA, et al. Role of platelet surface PF4 antigenic complexes in heparin-induced thrombocytopenia pathogenesis: diagnostic and therapeutic implications. Blood 2006;107(6): Kelton JG, Sheridan D, Santos A, et al. Heparin-induced thrombocytopenia: laboratory studies. Blood 1988;72(3): 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 1992;68(1):95 6.