The HITS Keep Coming Marc J. Kahn, MD, MBA, FACP Peterman-Prosser Professor Tulane University School...
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Transcript of The HITS Keep Coming Marc J. Kahn, MD, MBA, FACP Peterman-Prosser Professor Tulane University School...
![Page 1: The HITS Keep Coming Marc J. Kahn, MD, MBA, FACP Peterman-Prosser Professor Tulane University School of Medicine New Orleans, LA.](https://reader035.fdocuments.in/reader035/viewer/2022062713/56649cef5503460f949bd113/html5/thumbnails/1.jpg)
The HITS Keep Coming
Marc J. Kahn, MD, MBA, FACPPeterman-Prosser Professor
Tulane University School of MedicineNew Orleans, LA
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Clinical Case
You are asked to see a 43 year old women following bilateral elbow fractures with new onset thrombocytopenia. The patient suffered a fall in a dog park and sustained bilateral radial and ulnar fractures requiring open reduction. She has a history of antiphospholipid antibody syndrome and is maintained on warfarin. Her platelet count fell from 290K to 50 K over five days. She is asymptomatic.
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Definitions
• Lupus anticoagulant: prolongation of a clotting time (aPTT, DRVVT)
• Antiphospholipid Antibody: antibodies to cardiolipin, phospholipid, or b2GP1
• APLA Syndrome: thrombosis with APLA
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Lupus Anticoag Anti cardiolipin AB
Anti b2GP1
Anti phospholipid AB
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Antiphospholipid Antibody Syndrome
• High rate of arterial and venous thrombosis– 32% DVT– 9% PE– 13% CVA– 8% fetal loss
• 5-15% warfarin failure in preventing recurrence
Ann Rheum Dis. 2011
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Management of APLAS
• INR 2.0 to 3.0• INR 3.0 to 4.0 is NOT better*• Indefinite anticoagulation
*J Thromb Haemost. 2005;3:848-53.
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Thrombocytopenia and APLAb
• Estimated that up to 25% patients with thrombocytopenia may have APLAb
• Nearly 25% patients with APLAb have thrombocytopenia
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Our Patient’s Platelets
2-Nov
3-Nov
4-Nov
5-Nov
6-Nov
7-Nov
8-Nov
9-Nov
10-Nov
11-Nov
12-Nov
13-Nov
14-Nov
15-Nov
16-Nov
17-Nov
18-Nov
19-Nov
20-Nov
21-Nov
0
50
100
150
200
250
300
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DDx of Thrombocytopenia
• Drug induced• Heparin Induced• Sepsis/DIC• TTP• Catastrophic APLA syndrome• Not routine APLA due to sudden drop
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Copyright © 2011 American Society of Hematology. Copyright restrictions may apply.
John Lazarchick, ASH Image Bank 2011; 2011-1376
Peripheral smear
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Ruled out diagnosis
• TTP• DIC/Sepsis• Catastrophic APLAS
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Heparin Induced Thrombocytopenia
• Occurs 5 or more days after heparin therapy• Can occur faster in patients with prior
exposure (Warkentin NEJM 2001;344:1286)• estimated to occur in up to 3% patients
treated with unfractionated heparin• 24-fold increased relative risk of thrombosis
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Representative Case of Typical-Onset Heparin-Induced Thrombocytopenia, Followed by a Rapid-Onset Episode.
Warkentin TE, Kelton JG. N Engl J Med 2001;344:1286-1292.
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HITT pathophysiology
P
PF4 + heparin
IgG
Platelet activation, aggregation and clearance
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Aster RH. N Engl J Med 1995;332:1374-1376.
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Platelet factor 4 (PF4)
• Expressed in megakaryocytes• stored in platelet a-granules• highest heparin affinity of any platelet basic
protein derived compound• physiologic function remains unknown
– ? Role in thrombosis– ? Role in platelet recovery after radiation
• chemokine class of molecule
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4 T’s
• Thrombocytopenia (>50% fall)• Timing (5 to 10 days after heparin)• Thrombosis (new)• Thrombocytopenia from other causes• Very HIGH negative predictive value
J Thromb Haemost 2006;4:759
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HIT workup
• ELISA for heparin/platelet factor 4 antibodies– Sensitivity = >90%– Specificity = 24-90%
• Functional serotonin release assay– Sensitivity > 90%– Specificity>90%
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14C-serotonin release assay
+ 14C-serotonin + pt. serum + heparin
DPM
[heparin]0.1 0.2
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Management of HIT
• Need for anticoagulation• AVOID WARFARIN as initial therapy• Argatroban• Lepirudin• Bivalirudin (off-label)• Fondaparinux (off-label)
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Warfarin and HITT
• Associated with venous limb gangrene– Warkentin, et al. Ann Int Med 1997;127:804.
Factor Half-life (hrs)
II 72
VII 8
IX 24
X 39
Protein C 14
Protein S 42
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Argatroban
• Small molecule direct thrombin inhibitor• Licensed by FDA for HIT in 2000• IV infusion• Follow aPTT• Also increases PT• Metabolized by the liver
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Lepirudin (Refludan®)
• Direct thrombin inhibitor• Recombinant hirudin from medicinal leech• IV infusion• Follow aPTT• Cleared by the kidney
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Bivalirudin (Angiomax®)
• Direct thrombin inhibitor• Synthetic congener of naturally occurring
leech anticoagulant• IV infusion• Cleared by kidney• Follow aPTT• Not FDA approved for treatment of HIT
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Fondaparinux (Arixtra®)
• Synthetic pentasaccharide Xa inhibitor• subQ daily injection• Renal excretion• If monitoring necessary, anti Xa assay• Not FDA approved for treatment of HIT
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Low molecular weight heparin
antithrombin Factor Xa
Thrombin
Unfractionated heparin Low mol wt heparin
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Low molecular weight heparins
• Less likely to cause HIT than UFH• But, in one study, 62% of HIT cases caused by
dalteparin (Semin Thromb Hemost. 2011;37:653)
• Best avoided in setting of HIT
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Thrombosis in hospitalized patients
• HIT• APLA Syndrome• Trauma• Brain injury• Pelvic surgery• Orthopedic surgery• Pregnancy• Cancer
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VT Prevention in Medical Patients
• Importance of risk stratification• No difference in outcomes between LMWH
and UFH• Mechanical prophylaxis provided no benefit
with harm in stroke patients
Ann Int Med. 2011;155:602.
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Platelet transfusion
• Bleeding very uncommon in HIT• Transfused platelets can cause aggregation
and thrombosis• Platelet transfusions are to be avoided in HIT
unless significant bleeding
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Back to the Patient
Heparin-PF4 ELISA NEGATIVESerotonin Release Assay POSITIVEClinically consistent with HITTreated with Fondaparinux
When to start warfarin?
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Platelet counts
11-Nov
12-Nov
13-Nov
14-Nov
15-Nov
16-Nov
17-Nov
18-Nov
19-Nov
20-Nov
21-Nov
22-Nov
23-Nov
24-Nov
25-Nov
26-Nov
27-Nov
28-Nov
0
20
40
60
80
100
120
140
160
180
200
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Patient
• Warfarin started when platelet count normalized
• Fondaprinux stopped when INR >3.0• Patient D/C from hospital without thrombosis
or bleeding• Returned to work on warfarin
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How often do we need to monitor INR?
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Warfarin monitoring every 12 weeks is not inferior to monitoring every 4 weeks in patients on stable warfarin doses.
Schulman S, Parpia S, Stewart C, et al. Warfarin dose assessment every 4 weeks versus every 12 weeks in patients with stable international normalized ratios: a randomized trial. Ann Intern Med. 2011;155(10):653-9,
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12 week monitoring
• Patients stable for 6 months• Otherwise uncomplicated patients
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Pearls
• Antiphospholipid antibodies increase risk for arterial and venous thrombosis
• Typical patient with APLAS requires INR 2.0 to 3.0
• Clinical suspicion important in diagnosis HIT• AVOID WARFARIN with acute HIT• HIT requires anticoagulation
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Questions