PMID- 28856946
OWN - NLM
STAT- MEDLINE
DCOM- 20180515
LR  - 20220321
IS  - 1369-1635 (Electronic)
IS  - 0953-7104 (Linking)
VI  - 28
IP  - 6
DP  - 2017 Sep
TI  - Spontaneous HIT syndrome post-knee replacement surgery with delayed recovery of 
      thrombocytopenia: a case report and literature review.
PG  - 614-620
LID - 10.1080/09537104.2017.1366973 [doi]
AB  - Recently published reports have established a heparin-induced thrombocytopenia 
      (HIT)-mimicking thromboembolic disorder without proximate heparin exposure, 
      called spontaneous HIT syndrome. Although the pathophysiology remains unclear, 
      anti-platelet factor 4 (PF4)/heparin antibodies possibly triggered by exposure to 
      knee cartilage glycosaminoglycans or other non-heparin polyanions found on 
      bacterial surfaces and nucleic acids have been postulated. We present a 
      53-year-old female receiving antithrombotic prophylaxis with aspirin following 
      right total knee replacement surgery (without perioperative or any previous 
      lifetime heparin exposure) who acutely presented with high-risk pulmonary 
      embolism (PE) and right great saphenous vein thrombophlebitis on postoperative 
      day (POD) 14; her platelet count at presentation was 13 x 10(9)/L. Prior to 
      diagnostic consideration of spontaneous HIT syndrome, the patient briefly 
      received unfractionated heparin (UFH) and one dose of enoxaparin. The patient's 
      serum tested strongly positive for anti-PF4/heparin antibodies by two different 
      PF4-dependent enzyme-linked immunosorbent assays (ELISAs) and by serotonin 
      release assay (SRA). Failure of fondaparinux anticoagulation (persisting 
      HIT-associated disseminated intravascular coagulation) prompted switching to 
      argatroban. Severe thrombocytopenia persisted (platelet count nadir, 12 x 
      10(9)/L, on POD21), and 9 days after starting argatroban symptomatic right leg 
      deep-vein thrombosis (DVT) occurred, prompting switch to rivaroxaban. Thereafter, 
      her course was uneventful, although platelet count recovery was prolonged, 
      reaching 99 x 10(9)/L by POD45 and 199 x 10(9)/L by POD79. The patient's serum 
      elicited strong serotonin release in the absence of heparin (seen even with 1/32 
      serum dilution) that was enhanced by pharmacological concentrations of UFH (0.1 
      and 0.3 IU/mL) and fondaparinux (0.1-1.2 mug/mL, i.e., in vitro fondaparinux 
      "cross-reactivity"). Ultimately, platelet count recovery was associated with 
      seroreversion to a negative SRA (documented at POD151). Our literature review 
      identified joint replacement surgery, specifically knee replacement, to be a 
      relatively common trigger of spontaneous HIT syndrome. Further, including our 
      patient case, 5 of 7 patients with spontaneous HIT syndrome post-orthopedic 
      surgery who received treatment with argatroban developed new and/or progressive 
      lower-limb DVT or recurrent PE despite anticoagulation with this parenteral 
      direct thrombin inhibitor, suggesting that this patient population is at high 
      risk of breakthrough thrombotic events despite treatment with this HIT 
      treatment-approved anticoagulant. Our case also illustrates successful outcome 
      with rivaroxaban for treatment of spontaneous HIT syndrome, consistent with 
      emerging literature supporting safety and efficacy of direct oral anticoagulant 
      therapy for treatment of acute HIT.
FAU - Poudel, Dilli Ram
AU  - Poudel DR
AUID- ORCID: 0000-0003-2350-719X
AD  - a Reading Health System , West Reading , PA , 19612.
FAU - Ghimire, Sushil
AU  - Ghimire S
AD  - a Reading Health System , West Reading , PA , 19612.
FAU - Dhital, Rashmi
AU  - Dhital R
AD  - a Reading Health System , West Reading , PA , 19612.
FAU - Forman, Daniel A
AU  - Forman DA
AD  - a Reading Health System , West Reading , PA , 19612.
FAU - Warkentin, Theodore E
AU  - Warkentin TE
AUID- ORCID: 0000-0002-8046-7588
AD  - b Department of Pathology and Molecular Medicine, and Department of Medicine , 
      Michael G. DeGroote School of Medicine, McMaster University , Hamilton , Ontario 
      , Canada.
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Review
DEP - 20170831
PL  - England
TA  - Platelets
JT  - Platelets
JID - 9208117
RN  - 0 (Enoxaparin)
SB  - IM
MH  - *Arthroplasty, Replacement, Knee
MH  - Enoxaparin/administration & dosage/*adverse effects
MH  - Female
MH  - Humans
MH  - Middle Aged
MH  - *Postoperative Complications/blood/prevention & control
MH  - *Pulmonary Embolism/blood/prevention & control
MH  - *Thrombocytopenia/blood/chemically induced
MH  - *Thrombophlebitis/blood/prevention & control
OTO - NOTNLM
OT  - Argatroban
OT  - fondaparinux
OT  - knee replacement
OT  - rivaroxaban
OT  - spontaneous HIT syndrome
EDAT- 2017/09/01 06:00
MHDA- 2018/05/16 06:00
CRDT- 2017/09/01 06:00
PHST- 2017/09/01 06:00 [pubmed]
PHST- 2018/05/16 06:00 [medline]
PHST- 2017/09/01 06:00 [entrez]
AID - 10.1080/09537104.2017.1366973 [doi]
PST - ppublish
SO  - Platelets. 2017 Sep;28(6):614-620. doi: 10.1080/09537104.2017.1366973. Epub 2017 
      Aug 31.