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Case presentation delivered to pharmacy staff
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Heparin-Induced Thrombocytopenia: A Case Presentation
Darcie Gampetro
Pharm.D Candidate 2011
September 2010
Patient JB
Pt is a 45 y.o. female who presents with acute respiratory failure. Pt was recently hospitalized for possible BOOP and concomitant pseudomonas
infection (9/5-9/10)– Medications upon discharge:
TMP/SMX Ciprofloxacin Voriconazole *On 9/11 platelet count was 220,000
Social History:– Lives with husband and 15 year old son– Has 27 year old daughter– 30-pack-year smoking history– History of alcoholism-currently sober for 2 months
Allergies– Doxycycline– Fentanyl– Hydoxyzine– Ketorolac– Nalbuphine– NSAIDs
Patient JB
Chest x-ray showed worsening of bilateral diffuse interstitial infiltrates Significant lab values:
– BP=168/124– Pulse=127 – Respiratory rate=44– O2 saturation=49%– WBC=20.1– Hgb=9.6– Hct=28.2– plt:=138,000 platelets/μL – Scr=1.7– BUN=35– Glucose=256– BNP=361
Review of Systems:– Mostly unobtainable as pt was placed on Bipap
Height: 66 in Weight: 72.9 kg pH 7.23, pCO2 57, pO2 67, bicarb 24
JB Past Medical History
Type I Diabetes Mellitus Bronchiolitis Obliterans Organizing Pneumonia (BOOP) Cirrhosis with liver decompensation and renal insufficiency related to
alcoholism—complicated by steatohepatitis, fribrosis and coagulopathy Depression with anxiety-previous suicide attempt with drug overdose Anorexia Chronic abdominal pain Pancreatitis in 2007 Carpal tunnel surgery C-section two times Cholescystectomy in 2007 Tubal ligation Adenoidectomy in 2006 Colonoscopy in 2008
Home Medications
Guaifenesin 600mg po daily Trimethoprim sulfamethoxazole
1 DS tab daily Prednisone 30 mg po daily Mylanta 30 mL po prn Magic mouthwash 30 mL po prn Voriconazole 200 mg po q12h Nicoderm 7 mg patch daily Methadone 60 mg po tid with
meals Ciprofloxacin 500 mg po bid Ursodiol 300 mg po tid Oxycodone 5 mg 2-3 tablets po
tid prn Omeprazole 40 mg po daily Vitamin E 1000 units po daily
Glucagon 1 mg subcutaneously one time as needed
Vitamin D 50,000 unitis po q 7 days
Lantus 32 units subcutaneously daily qam
Promethazine 25 mg tid prn Lorazepam 0.5 mg po bid prn Polyethylene glycol one 17 gm
packet po daily prn Metoclopramide 10 mg po qid
prn Multivitamin one tablet po daily Novolog correction scale
Inpatient Medications Day 1
Furosemide Methadone Lansoprazole Phyontadione Albuterol
Guaifenesin Propofol Hydromorphone Methylprednisolone Insulin Enoxaparin
Day 2 Medication Changes
Enoxaparin changed to heparin due to hepatic decompensation and renal insufficiency
Pipercillin/Tazobactam added Esomeprazole added Metoclopramide added
Day 4
4 doses of heparin given from 9/14-9/15 Platelets:
– 9/14: 104,000 platelets/μL– 9/15: 94,000 platelets/μL– 9/16:78,000 platelets/μL
Heparin-Induced Thrombocytopenia
Topic Discussion
Heparin-Induced Thrombocytopenia (HIT)
Decreased platelet count during or following heparin therapy
– <150,000 platelets/μL– 50% decrease from baseline
Onset may be rapid or delayed Mechanism of immune response
– Heparin binds to platelet factor 4 (PF4)
– IgG, IgM, and IgA antibodies generated
– Complexes aggregate and are prematurely removed from circulationthrombocytopenia
– Platelet activation leads to prothrombotic platelet microparticlespromotes coagulation
Two types of HIT– Type 1
Benign form Small decrease in platelet
count occurring two days after initiation of heparin (platelet count usually >100,000 platelets/μL)
Platelet counts return to normal with continued heparin therapy
– Type 2 More serious form of HIT Immune-mediated disorder
with formation of antibodies against heparin-PF4 complex
Risk of thrombosis
Figure taken from Uptodate (see references
Type 2 HIT
Factors strongly associated with development of HIT– Long duration of therapy ( >4 days)– Use of UFH– Surgery patients – Female rather than male pts
Thrombotic risk from HIT is more than 30x that of control population
Risk of thrombus remains high for days to weeks
Diagnosis of HIT
Rule out other causes of thrombocytopenia– Bacterial infection– Medications– Bone marrow disease
Laboratory Diagnosis– What abnormal values would we expect?
Pretest Probability of HITThe 4 T’s
Thrombocytopenia Timing of platelet count fall Thrombosis Other causes for thrombocytopenia present?
The 4 T’sThrombocytopenia
Platelet count fall > 50% and nadir >20,000: 2 points
Platelet count fall 30-50% or nadir 10-19,000: 1 point
Platelet count fall <30% or nadir <10,000: 0 points
The 4 T’sTiming of platelet count fall
Clear onset on days 5-10 or platelet count fall ≤1 day if previous heparin exposure within last 30 days:2 points
Not clear fall on days 5-10 (missing platelet counts) or onset after day 10 or fall ≤1 day with previous heparin exposure within last 30-100 days:1 point
Platelet count fall at <4 days without recent exposure:0 points
The 4 T’s Thrombosis or other sequelae
Confirmed new thrombosis, skin necrosis, or acute systemic reaction after IV UFH bolus: 2 points
Progressive or recurrent thrombosis, non-necrotizing skin lesions, or suspected thrombosis which has not been proven:1 point
None:0 points
The 4 T’sOther causes for thrombocytopenia present
None apparent: 2 points Possible: 1 point Definite: 0 points
The 4 T’s Score
Zero to 3: Low probability 4 to 5: Intermediate probability 6 to 8: High probability
Clinical Presentation
What are the clinical manifestations of HIT? Implications
– Mortality in 20-30% of patients with thrombosis – 20-30% of patients will become permanently
disabled
Treatment
Cessation of all formulations of heparin Alternative anticoagulation
– Lepirudin (Refludan®)– Bivalirudin (Angiomax ®)– Argatroban– Fondiparinux– Warfarin-once anticoagulated with other agent and platelets
>150,000/μL Duration of anticoagulation
– Two to three months if no thrombotic event occurred– Six months if thrombotic event occurred
Lepirudin (Refludan®)
Recombinant Hirudin Direct thrombin inhibitor FDA labeled indication: anticoagulation in patients with HIT and
associated thromboembolic disease in order to prevent further thromboembolic complications
Dosing: – Bolus: 0.4 mg/kg IVP over 15-20 seconds (max=44 mg)– Maintenance: 0.15 mg/kg/hr (16.5 mg/hr)– Reduce dose in renal impairment– Goal aPTT= 1.5-2.5 above baseline
For conversion to oral anticoagulant, must be above 1.5x aPTT and overlap therapies 4 to 5 days
Bivalirudin (Angiomax®)
Thrombin inhibitor FDA labeled indications: anticoagulant used in conjunction with
aspirin for patients with unstable angina undergoing percutaneous transluminal coronary angioplasty with provisional glycoprotein IIb/IIIa inhibitor; anticoagulant used in PCI or in patients at risk for HIT
Dosing:– Bolus: 0.75 mg/kg – Maintenance: 1.75 mg/kg/hr continuous infusion for up to 4 hours– If need further therapy, give 0.2 mg/kg/hr for up to 20 hours– Reduce dose in renal impairment
Argatroban
Direct thrombin inhibitor FDA labeled indications: prophylaxis or treatment of thrombosis
in patients with HIT; adjunct to percutaneous coronary intervention in patients who have or are at risk of thrombosis associated with HIT
Dosing:– 2mcg/kg/min IV– Goal aPTT at steady state is 1.5-3 times the initial baseline
value Can be used in patients with ESRD
Fondaparinux (Arixtra®)
Factor Xa inhibitor Not approved for use in HIT Dosing:
– 2.5 mg once daily
Long half life Renaly eliminated
Back to the case…
What tests should be done in this patient? What is our patients 4 T’s Score? Is it likely to be HIT? If so, what type? What are the options for anticoagulation in
this patient?
Back to the case…
Lab test ordered on 9/15 to determine presence of antibodies to heparinoid and PF4 complexes
On 9/16:– heparin was discontinued– Pt received blood transfusion (2 units)
On 9/17:– platelet count decreased to 65,000 platelets/μL.
On 9/18:– Serology testing revealed 48% heparin dependent platelet
antibiody reactivity– agatroban therapy was initiated.– platelet count rose to 80,000 platelets/μL
Patient’s platelet count continues to rise 122,000 platelets/μL
Back to the case…
What tests should be done in this patient?– Platelets– Serum reactivity
What is our patients 4 T’s Score?– Thrombocytopenia (1 point)+ Timing (0 points) + thrombosis or
other sequelae (0 points) + Other causes (1 point)= 2 points Is it likely to be HIT? If so, what type?
– 4 T’s score <3– Occurred within 2 days – Platelet count was trending down previously– Pt has hepatic insufficiency and coagulopathy issues
What other options for anticoagulation in this patient could be considered?
St. Luke’s Policy
References
Diaz, Josephina, et al. "Profiling of heparin-induced thrombocytopenia antibody levels in patients with and without diabetes." Clinical and applied thrombosis/hemostasis 16.2 (2010):121-5.
Franchini, Massimo. "Heparin-induced Thrombocytopenia: an Update." Thrombosis Journal. 04 Oct. 2005. Web. 20 Sept. 2010. <http://www.thrombosisjournal.com/content/3/1/14>.
Arepally, Gowthami M., and Thomas L. Ortel. "Heparin-Induced Thrombocytopenia." New England Journal of Medicine 355.8 (2006): 809-17. 24 Aug. 2006. Web. 20 Sept. 2010
Coutre, Steven. "Heparin-Induced Thrombocytopenia." UpToDate Inc. 28 Jan. 2008. Web. 23 Sept. 2010. <http://www.uptodate.com/online/content/topic.do?topicKey=coagulat/8950&selectedTitle=1~150&source=search_result>.
DiPiro, Joseph T. "Hematologic Disorders." Pharmacotherapy: a Pathophysiologic Approach. New York: McGraw-Hill Medical, 2008. 1875-889. Print.
Micromedex DrugDex Index Search Term: Lepirudin Micromedex DrugDex Index Search Term: Bivalirudin Micromedex DrugDex Index Search Term: Argatroban Micromedex DrugDex Index Search Term: Fondaparinux Lexi-Drugs Search Term: Lepirudin Lexi-Drugs Search Term: Bivalirudin Lexi-Drugs Search Term: Argatroban Lexi-Drugs Search Term: Fondaparinux