Intricacies Of Treating Heparin Induced Thrombocytopenia With Preexisting Antiphospholipid Syndrome and Renal Insufficiency

Treatment of heparin induced thrombocytopenia (HIT) requires the use of alternatives anticoagulants, such as a direct thrombin inhibitor – argatroban. Use of argatroban relies on frequent laboratory monitoring of the activated partial thromboplastin time (aPTT) to maintain an adequate level of anticoagulation. This requirement poses a challenge in patients with prolonged baseline aPTT, such as in antiphospholipid syndrome. While other assays are being explored they require an extended turn around time because of their limited availability. We present a case of a 63 year old male with a history of antiphospholipid syndrome, end stage renal disease on hemodialysis, hepatitis C, and on long term anticoagulation with warfarin for cerebral vein thrombosis. His hospital course required transition to unfractionated heparin and subsequently developed thrombocytopenia. A heparin-platelet factor 4 ELISA antibody assay was performed for an intermediate clinical likelihood of HIT and returned positive. Although not confirmed with the gold standard serotonin release assay (SRA), clinical suspicion for HIT obligated treatment with an alternative anticoagulant. Conventional dosing and administration of argatroban however could not be performed because of the patient’s prolonged baseline aPTT. Other agents such as fondaparinux were also not possible in the setting of renal insufficiency. Short of other treatment techniques accepted in this unique set of circumstances we practiced a fixed dose argatroban (0.5 mcg/kg/min for Child’s class B cirrhosis). The patient tolerated the empiric dosing well until discontinued because of a negative SRA. This case demonstrates the limitations of current treatment recommendations of HIT and need for further investigation in similar patients. Disclosures: No relevant conflicts of interest to declare.

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Diagnosis and treatment of heparin-induced thrombocytopenia

Perfusion ◽

10.1191/0267659103pf637oa ◽

2003 ◽

Vol 18 (1) ◽

pp. 47-53 ◽

Cited By ~ 6

Author(s):

William J DeBois ◽

Junli Liu ◽

Leonard Y Lee ◽

Leonard N Girardi ◽

Charles Mack ◽

...

Keyword(s):

New York ◽

Platelet Inhibition ◽

Heparin Therapy ◽

Serotonin Release ◽

Antibody Detection ◽

Thrombin Inhibitor ◽

Heparin Infusion ◽

Platelet Factor ◽

Heparin Induced Thrombocytopenia ◽

Life Threatening

Heparin-induced thrombocytopenia (HIT) is a major side effect secondary to the administration of heparin. This syndrome is serious and potentially life threatening. This response is the result of antibodies formed against the platelet factor 4 (PF4)/heparin complex. The incidence of this immune-mediated syndrome has been estimated to be 1-3% of all patients receiving heparin therapy. The occurrence of HIT in patients requiring full anticoagulation for cardiopulmonary bypass (CPB), therefore, presents a serious challenge to the cardiac surgery team. The diagnosis of HIT should be based on both clinical and laboratory evidence. While functional assays, platelet aggregation tests, and the serotonin release assay can be used to support the diagnosis, the negative predictive value of these tests is generally less than 50%. In contrast, although non-functional antibody detection assays are more sensitive, they have a low specificity. HIT can be treated in several ways, including cessation of all heparin and giving an alternative thrombin inhibitor, platelet inhibition followed by heparin infusion, and the use of low molecular weight heparins. In this presentation, the pathology and current diagnostic tests, as well as the successful management of patients with HIT undergoing CPB at New York Presbyterian Hospital, are reviewed.

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Incidence of Heparin Induced Thrombocytopenia in the Transplant Population: A Large Retrospective Cohort, Single Transplant Centre Experience

Blood ◽

10.1182/blood.v120.21.3320.3320 ◽

2012 ◽

Vol 120 (21) ◽

pp. 3320-3320

Author(s):

Syed Hassan ◽

Dania Khoulani ◽

Ami Badami ◽

Zaid Alirhayim ◽

Mohamad A. Younes ◽

...

Keyword(s):

Retrospective Cohort ◽

Conflicts Of Interest ◽

Organ Transplant ◽

Serotonin Release ◽

Confirmatory Test ◽

Thrombin Inhibitor ◽

Thromboembolic Events ◽

Transplant Recipients ◽

Heparin Induced Thrombocytopenia ◽

Transplant Patients

Abstract Abstract 3320 Objective: Heparin induced thrombocytopenia (HIT), a prothrombotic complication of heparin therapy, can lead to serious thromboembolic events and cause significant morbidity and mortality. Its occurrence has never been studies in transplant patients, where use of heparin products is very common. We aim to study its prevalence in the transplant population at our institute. Methods: This is a retrospective cohort, single center study which looked into the clinical and laboratory database of all the patients that has undergone any kind of transplant at our institution over a period of 25 years (January 1985 - December 2010). In patients with clinical suspicious of HIT, a pre-test probability was calculated using the 4T scoring system. Results of the laboratory test like the ELISA HIT antibody (HIT ab) test and the functional serotonin release assay test (SRA) along with clinical manifestation of skin necrosis or thromboembolic events were reviewed. Results: Medical records of 2800 patients that has undergone transplant from January 1985- December 2010 were reviewed. HIT antibody assay was performed in 262 patients in which HIT was suspected. Of these, only 48 (18%) patients (mean age 57 ± 11 years, 71% women) had HIT ab positive, 9 were pre transplant recipient and remaining 39 were post transplant recipients. Baseline characteristics of the transplant population are illustrated in Table.1. Confirmatory test, SRA was performed in 8 HIT antibody positive patients, of whom only 4 were positive. The mean 4T score in HIT suspected patients was 3.7 ±1.3, while the score in HIT ab positive patients was 4.2 ± 1.2. Thrombotic complications were seen in 11(0.4%) patients, with the highest incidence rate of 1% in heart transplant recipients. No transplant patient had skin manifestations. Direct Thrombin inhibitor (DTI) was used only in 5 patients who had thrombotic events. No other complication or mortality was reported in any of the HIT ab positive transplant patients. Conclusion: To our knowledge, this is the first study of its kind that has shown very low incidence of HIT in transplant population. In conclusion, transplant patients can safely undergo any type of organ transplant, without having any peri or post operative complications or immediate mortality related to HIT. Disclosures: No relevant conflicts of interest to declare.

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Heparin-Induced Thrombocytopenia: A Rapid, Reliable and Practical, Functional Flow-Cytometric Assay

Blood ◽

10.1182/blood.v122.21.1130.1130 ◽

2013 ◽

Vol 122 (21) ◽

pp. 1130-1130

Author(s):

Varda Deutsch ◽

Michal Cipok ◽

Sigi Kay ◽

Yvette Levy ◽

Shoshana Bar On ◽

...

Keyword(s):

Conflicts Of Interest ◽

High Sensitivity ◽

Relative Sensitivity ◽

Serotonin Release ◽

Specific Test ◽

Platelet Factor ◽

Heparin Induced Thrombocytopenia ◽

Laboratory Confirmation ◽

Relative Specificity ◽

Biological Probe

Abstract Background Heparin-induced thrombocytopenia (HIT) is a serious complication of heparin treatment, associated with morbidity and mortality. HIT is characterized by thrombocytopenia and thrombotic complications secondary to the formation of antibodies (Abs) against heparin-platelet-factor 4 (PF4) complexes. The pathologic mechanism involves the binding of the heparin-immune-complex to the platelet-Fc-receptor, resulting in platelet activation, aggregation, and rapid elimination. The diagnosis of HIT requires laboratory confirmation. Common laboratory testing is based on immune detection of antibodies directed against the PF4/heparin complex (ID-H/PF4-PaGIA or ELISA). However, these assays suffer from methodological limitations, especially low specificity, as compared to the platelet functional assays. The “gold standard” functional test for detecting of platelet-activating antibodies is the radioactive [14C] serotonin-release assay (14C-SRA) (Sheridan D, et al, Blood. 1986;67:27-30, Kelton JG, et al.,Blood.1988;72:925-30). However, the assay includes the use of a radiolabeled biological probe and requires considerable expertise to obtain reliable results. Consequently, its use is limited to research laboratories. Aim To overcome the methodological limitations associated with current assays, we modified a functional flow-cytometry assay (FCA), which exhibits high sensitivity and specificity (Tomer, A. Br J Haematol, 1997;98: 648-656 , Tomer, A., et al, Am J Hematol, 1999;61: 53-61). This assay, similar in concept to the 14C-SRA, determines the capacity of the patient's serum to activate platelets in the presence of heparin, using a fluorescent probe. Methods Consecutive samples from 254 patients clinically suspected for HIT were tested. The FCA assay was compared with the standard ID-H/PF4-PaGIA antigenic assay (DiaMed, Switzerland) with two dilutions to assess specificity (Nellen, V., et al.,Haematologica, 2012;97: 89-97). Results Of the total 254 samples tested, 48 (19%) were positive by PaGIA, compared to 13 (5.1%) positive by the functional FCA (Table 1). The number of PaGIA positive samples was reduced to 24 (9.4%) by 1:16 dilution, and to 14 (5.5%) by 1:32 dilution. All FCA positive samples were positive at all PaGIA dilutions (relative sensitivity 93%). Thirty PaGIA negative samples were all negative by the FCA (relative specificity 100%). Conclusion The results suggest that the functional FCA is a practical, sensitive, and highly specific test for the reliable diagnosis of HIT. Disclosures: No relevant conflicts of interest to declare.

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Pathophysiology of Heparin-Induced Thrombocytopenia

Archives of Pathology & Laboratory Medicine ◽

10.5858/2000-124-1657-pohit ◽

2000 ◽

Vol 124 (11) ◽

pp. 1657-1666 ◽

Cited By ~ 4

Author(s):

Fabrizio Fabris ◽

Sarfraz Ahmad ◽

Giuseppe Cella ◽

Walter P. Jeske ◽

Jeanine M. Walenga ◽

...

Keyword(s):

Platelet Activation ◽

Serotonin Release ◽

Platelet Factor 4 ◽

Thrombin Inhibitors ◽

Platelet Factor ◽

Cellular Activation ◽

Heparin Induced Thrombocytopenia ◽

New Information ◽

Study Selection ◽

Release Assay

Abstract Objective.—This review of heparin-induced thrombocytopenia (HIT), the most frequent and dangerous side effect of heparin exposure, covers the epidemiology, pathophysiology, clinical presentation, diagnosis, and treatment of this disease syndrome. Data Sources and Study Selection.—Current consensus of opinion is given based on literature reports, as well as new information where available. A comprehensive analysis of the reasons for discrepancies in incidence numbers is given. The currently known mechanism is that HIT is mediated by an antibody to the complex of heparin–platelet factor 4, which binds to the Fc receptor on platelets. New evidence suggests a functional heterogeneity in the anti-heparin-platelet factor 4 antibodies generated to heparin, and a “superactive” heparin-platelet factor 4 antibody that does not require the presence of heparin to promote platelet activation or aggregation has been identified. Up-regulation of cell adhesion molecules and inflammatory markers, as well as preactivation of platelets/endothelial cells/leukocytes, are also considered to be related to the pathophysiology of HIT. Issues related to the specificity of currently available and new laboratory assays that support a clinical diagnosis are addressed in relation to the serotonin-release assay. Past experience with various anticoagulant treatments is reviewed with a focus on the recent successes of thrombin inhibitors and platelet GPIIb/IIIa inhibitors to combat the platelet activation and severe thrombotic episodes associated with HIT. Conclusions.—The pathophysiology of HIT is multifactorial. However, the primary factor in the mediation of the cellular activation is due to the generation of an antibody to the heparin-platelet factor 4 complex. This review is written as a reference for HIT research.

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Serologic Results in >1000 Patients With Suspected Heparin-Induced Thrombocytopenia

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/1076029607304721 ◽

2007 ◽

Vol 14 (4) ◽

pp. 410-414 ◽

Cited By ~ 8

Author(s):

Suresh G. Shelat ◽

Anne Tomaski ◽

Eleanor S. Pollak

Keyword(s):

Laboratory Diagnosis ◽

Serotonin Release ◽

Enzyme Linked Immunosorbent Assay ◽

Functional Assay ◽

Platelet Factor ◽

Heparin Induced Thrombocytopenia ◽

Life Threatening ◽

Release Assay ◽

Pathogenic Antibodies

Heparin-induced thrombocytopenia (HIT) can lead to life-threatening and limb-threatening thrombosis. HIT is thought to be initiated by the interaction of pathogenic antibodies toward a complex platelet factor 4 (PF4) and heparin (PF4:H), which can activate platelets and predispose to thrombosis. As such, the laboratory diagnosis of HIT includes antigenic and functional assays to detect antibodies directed at PF4:H complexes. We performed a retrospective analysis of 1017 consecutive samples tested by serotonin-release assay and by enzyme-linked immunosorbent assay (ELISA). Most samples showed no serologic evidence of HIT, whereas 4% to 5% of samples demonstrated both antigenic and functional serological evidence for HIT. Approximately 12% to 18% of samples showed immunologic evidence of anti-PF4:H antibodies but without functional evidence of serotonin release in vitro. Interestingly, a small minority of samples (0.7%) caused serotonin release but were negative in the ELISA. The results are presented using cutoff values established at our hospital and for the ELISA manufacturer. This study provides a pretest probability of the serologic results from an antigenic assay (ELISA) and a functional assay (serotonin-release assay) in patients clinically suspected of having HIT.

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Heparin-Induced Thrombocytopenia (HIT): A Rural Community Based Experience.

Blood ◽

10.1182/blood.v110.11.3925.3925 ◽

2007 ◽

Vol 110 (11) ◽

pp. 3925-3925

Author(s):

N. Mullai ◽

Amanda Brock ◽

Shona Harper

Keyword(s):

Rural Community ◽

Rapid Test ◽

Heparin Therapy ◽

Serotonin Release ◽

Rural Setting ◽

Thrombin Inhibitor ◽

Test Results ◽

Community Based ◽

Heparin Induced Thrombocytopenia ◽

Release Assay

Abstract Background: Heparin-induced thrombocytopenia (HIT) is a known complication of heparin therapy. This study was planned to assess the experience of a community based medical practice with HIT in a rural setting. Method: A retrospective study was done from medical records of patients suspected clinically of HIT from January 2006 to January 2007. The data were analyzed with regard to test results of patients, especially those who were positive for the HIT antibody and correlated with national statistics. Result: Fifty-two (52) patients were suspected clinically of having HIT during the study period. All 52 patients received heparin and most of them had cardiac surgery before the onset of thrombocytopenia. Six out of fifty-two (6/52) patients were found to have positive HIT antibody. Two out of six (2/6) also had positive serotonin release assay. Two out of six (2/6) developed heparin-induced thrombocytopenia with thrombosis (HITT). One of the two patients with HITT died of complications. The range of time to obtain test results was 5–7 days. Four out of fifty-two (4/52) patients received thrombin inhibitor lepirudin (Refludan) as alternate anticoagulation. Conclusion: The overall incidences, time of onset, relation to heparin treatment were similar to that of national averages. The time to obtain diagnostic test results ranged 5–7 days and heparin was withheld in all of them, and more expensive anticoagulation was used for some of them while waiting for the test results. This dilemma in diagnosis and treatment could be avoided if a rapid test that can help to assess the risk early in about 12–24 hrs, is possible. Such a test would be very beneficial especially in small, rural community settings where the availability of expensive testing and medications for HIT are limited.

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Polymorphisms in TNFA and CTLA-4 Genes and the Risk of Heparin Induced Thrombocytopenia.

Blood ◽

10.1182/blood.v112.11.3414.3414 ◽

2008 ◽

Vol 112 (11) ◽

pp. 3414-3414

Author(s):

Dorothee Leroux ◽

Claire Pouplard ◽

Benoit Guillet ◽

Beatrice Cosne ◽

Marc Antoine May ◽

...

Keyword(s):

Heart Surgery ◽

Cytotoxic T Lymphocyte ◽

Rflp Analysis ◽

Serotonin Release ◽

Nucleotide Polymorphisms ◽

Platelet Factor ◽

Heparin Induced Thrombocytopenia ◽

Significant Difference ◽

Patients At Risk ◽

High Doses

Abstract Backgroud and objectives: The formation of antibodies (Abs) to heparin platelet factor 4 complexes (H/PF4) associated with heparin-induced thrombocytopenia (HIT) is a T-helper cell dependent event that involves antigen presenting cells (APC) and B-lymphocytes. Polymorphisms of the CTLA-4 (cytotoxic T lymphocyte antigen 4) gene have been described as a risk factor in several autoimmune diseases. In addition, TNFα is a major inflammatory cytokine with potent regulatory functions and polymorphisms in TNFA have also been associated with autoimmune antibody-mediated diseases. We therefore evaluated the possibility that an association between polymorphisms in CTLA-4 (−318 C/T and +49 A/G) or TNFA (−308 G/A) and the development of Abs to H/PF4 and HIT might exist. Methods: Eighty-three patients identified as having developed definite HIT with significant levels of Abs to PVS/PF4 in ELISA (HAT 45, GTI, Brookfield, WI, USA) and positive serotonin release assay were studied (HIT group). Two control groups were studied: the Abneg group consisted of 83 patients who had undergone heart surgery with high doses of unfractionated heparin administered during cardiopulmonary bypass (CPB), and who were tested negative for Abs to PVS/PF4 at the 8th post operative day. The Abpos group consisted of 58 patients who had also undergone CPB but had developed high levels of Abs to PVS/PF4 without significant change in the platelet count post-operatively. Three single nucleotide polymorphisms (SNPs), one in TNFA (−308G/A) and two in CTLA-4 (−318 C/T and +49A/G) were studied by conventional RFLP analysis as described (Astermark et al, Blood 2006 and Astermark et al, Thromb Haemost 2007). Results: The CTLA-4 +49 A/G and −318 C/T genotypes and allele distributions were similar in the 3 groups of patients (Table). In contrast, the frequency of TNFA –308 G/G homozygotes was higher in the HIT group compared to patients without HIT whether they had developed PF4-specific Abs or not (p=0.035). Therefore, the A allele was less frequent in HIT patients (p=0.026, OR 0.49; CI95% 0.26–0.93) but there was no significant difference when comparing patients with and without PF4-dependent antibodies. Genotype Allele frequency Ab neg (n = 82) Ab pos (n = 58) HIT (n = 82) CTLA-4(+49) A/A 31 (38%) 24 (41%) 35 (43%) A/G 40 (49%) 26 (45%) 41 (50%) G/G 11 (13%) 8 (14%) 6 (7%) CTLA-4(−318) C/C 63 (77%) 49 (84%) 67 (82%) C/T 19 (23%) 9 (16%) 17 (21%) T/T 0 0 0 (0%) TNFα(−308) G/G 59 (72%) 41 (71%) 68 (84%) G/A 20 (24%) 15 (26%) 12 (15%) A/A 3 (4%) 2 (3%) 1 (1%) A Allele 0.160 0.160 0.09 G Allele 0.840 0.840 0.910 Conclusion: The TNFA –308 A allele appears to be protective regarding the risk of heparin-induced thrombocytopenia in patients having developed PF4-specific antibodies. A similar effect has been suggested in immune thrombocytopenic purpura (Foster et al, Brit J Haematol 2001) despite individuals with this allele have been identified as high TNFα producers. Therefore, the mechanisms involved for explaining this apparent protective effect of the TNFA −308A allele in patients at risk for HIT have to be identified.

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Comparison of an IgG-Specific Enzyme-Linked Immunosorbent Assay Cutoff of 0.4 Versus 0.8 and 1.0 Optical Density Units for Heparin-Induced Thrombocytopenia

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/1076029615606532 ◽

2016 ◽

Vol 23 (3) ◽

pp. 282-286 ◽

Cited By ~ 5

Author(s):

Brianne M. Ritchie ◽

Jean M. Connors ◽

Katelyn W. Sylvester

Keyword(s):

Optical Density ◽

Immunosorbent Assay ◽

Predictive Value ◽

Retrospective Chart Review ◽

Serotonin Release ◽

Enzyme Linked Immunosorbent Assay ◽

Platelet Factor ◽

Heparin Induced Thrombocytopenia ◽

Institutional Review ◽

Sensitivity Specificity

Background: Previous studies have demonstrated optimized diagnostic accuracy in utilizing higher antiheparin–platelet factor 4 (PF4) enzyme-linked immunosorbent assay (ELISA) optical density (OD) thresholds for diagnosing heparin-induced thrombocytopenia (HIT). We describe the incidence of positive serotonin release assay (SRA) results, as well as performance characteristics, for antiheparin–PF4 ELISA thresholds ≥0.4, ≥0.8, and ≥1.0 OD units in the diagnosis of HIT at our institution. Methods: Following institutional review board approval, we conducted a single-center retrospective chart review on adult inpatients with a differential diagnosis of HIT evaluated by both antiheparin–PF4 ELISA and SRA from 2012 to 2014. The major endpoints were to assess incidence of positive SRA results, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy at antiheparin–PF4 ELISA values ≥0.4 OD units when compared to values ≥0.8 and ≥1.0 OD units. Clinical characteristics, including demographics, laboratory values, clinical and safety outcomes, length of stay, and mortality, were collected. Results: A total of 140 patients with 140 antiheparin–PF4 ELISA and SRA values were evaluated, of which 23 patients were SRA positive (16.4%) and 117 patients were SRA negative (83.6%). We identified a sensitivity of 91.3% versus 82.6% and 73.9%, specificity of 61.5% versus 87.2% and 91.5%, PPV of 31.8% versus 55.9% and 63.0%, NPV of 97.3% versus 96.2% and 94.7%, and accuracy of 66.4% versus 86.4% and 88.6% at antiheparin–PF4 ELISA thresholds ≥0.4, ≥0.8, and ≥1.0 OD units, respectively. Conclusion: Our study suggests an increased antiheparin–PF4 ELISA threshold of 0.8 or 1.0 OD units enhances specificity, PPV, and accuracy while maintaining NPV with decreased sensitivity.

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Spontaneous Heparin-Induced Thrombocytopenia and COVID-19 Infection

Blood ◽

10.1182/blood-2021-151590 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 4216-4216

Author(s):

Suneetha Amara

Keyword(s):

Platelet Count ◽

Conflicts Of Interest ◽

Hospitalized Patients ◽

Target Range ◽

Low Grade ◽

Primary Therapy ◽

Platelet Factor ◽

Heparin Induced Thrombocytopenia ◽

The Right ◽

D Dimer

Abstract Background and Objective: Heparin-induced thrombocytopenia (HIT) can develop if immune responses to infections become pathologic in the presence of heparins. Low molecular weight heparin or unfractionated heparin are recommended for prophylaxis and treatment of venous thromboembolic disease in hospitalized patients with Covid-19 infection but may trigger HIT. Our aim is to alert clinicians that HIT occurs in association with Covid-19 infections even in the absence of prior exposure and may not be easily recognized without a high index of suspicion. Case Summary: A 33-year-old previously healthy male was initially evaluated for low grade fever, dyspnea without hypoxia and cough. A Covid-19 PCR swab was negative despite a recent exposure. He was treated with azithromycin. However, his symptoms did not improve, he then developed right leg swelling and hypoxia, so he was re-evaluated. CTA of the chest showed bilateral pulmonary emboli and ground-glass opacities at the lung bases. Venous Duplex Ultrasound showed non-occlusive thrombus in the deep veins of right lower extremity. He was hospitalized and placed on oxygen and heparin. Covid-19 swab was negative again. Laboratory tests before heparin showed a decreased platelet count of 64,000 k/ul, elevated prothrombin time of 16.4 seconds, normal aPTT at 30.8 seconds, decreased serum fibrinogen at 120 mg/dl and markedly elevated D-dimer at 59,966 ng/ml. Lupus anticoagulant and anti-phospholipid antibody tests were negative. On heparin at the desired therapeutic aPTT target range, the right leg became significantly swollen and painful by day five. Platelet count had decreased further to 39,000 k/ul. Repeat doppler examination of the right leg now showed more severe and extensive deep venous thrombosis. D-dimer had increased to 125,133 ng/ml. The HIT 4T score was 4, suggesting intermediate probability. Rapid HIT immunoassays on 2 separate samples were positive. Heparin was discontinued and he was placed on argatroban. Serotonin release assays on 2 separate samples came back positive. Suspicion for Covid-19 infection remained high and so a Covid-19 serology sample was obtained which was positive for IgG. A repeat nasopharyngeal swab at this time turned positive. He did not receive any COVID specific treatments. As viability of his leg appeared threatened, he underwent right iliofemoral vein thrombectomy with arteriovenous fistula creation. He improved on argatroban and was transitioned to apixaban with gradual normalization of hemostasis laboratory parameters, improvement in hypoxemia and fading clinical symptoms, he was discharged home on day 15. Conclusion: Current consensus guidelines for thromboprophylaxis and treatment of thromboembolism in hospitalized patients with Covid-19 infection recommend heparins as primary therapy to reduce morbidity and mortality. However, our report in addition to the two previous reports of HIT in Covid-19 patients illustrate that HIT can be a complication in the setting of Covid-19 infection. Further, our report also highlights that HIT with thrombosis can occur in a spontaneous manner in the absence of prior heparin exposure, which has been so far studied only in bacterial infection with the hypothesis that Platelet factor 4 (PF4) can bind to negatively charged polysaccharides on the surface of bacteria, triggering an immune response. Disclosures No relevant conflicts of interest to declare.

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Heparin-induced thrombocytopenia and cardiovascular surgery

Hematology ◽

10.1182/hematology.2021000289 ◽

2021 ◽

Vol 2021 (1) ◽

pp. 536-544

Author(s):

Allyson M. Pishko ◽

Adam Cuker

Keyword(s):

Cardiac Surgery ◽

Antiplatelet Agent ◽

Serotonin Release ◽

Functional Assay ◽

Platelet Factor ◽

Heparin Induced Thrombocytopenia ◽

Heparin Complexes ◽

Institutional Experience ◽

History Of ◽

Postoperative Setting

Abstract Clinicians generally counsel patients with a history of heparin-induced thrombocytopenia (HIT) to avoid heparin products lifelong. Although there are now many alternative (nonheparin) anticoagulants available, heparin avoidance remains challenging for cardiac surgery. Heparin is often preferred in the cardiac surgery setting based on the vast experience with the agent, ease of monitoring, and reversibility. To “clear” a patient with a history of HIT for cardiac surgery, hematologists must first confirm the diagnosis of HIT, which can be challenging due to the ubiquity of heparin exposure and frequency of thrombocytopenia in patients in the cardiac intensive care unit. Next, the “phase of HIT” (acute HIT, subacute HIT A/B, or remote HIT) should be established based on platelet count, immunoassay for antibodies to platelet factor 4/heparin complexes, and a functional assay (eg, serotonin release assay). As long as the HIT functional assay remains positive (acute HIT or subacute HIT A), cardiac surgery should be delayed if possible. If surgery cannot be delayed, an alternative anticoagulant (preferably bivalirudin) may be used. Alternatively, heparin may be used with either preoperative/intraoperative plasma exchange or together with a potent antiplatelet agent. The optimal strategy among these options is not known, and the choice depends on institutional experience and availability of alternative anticoagulants. In the later phases of HIT (subacute HIT B or remote HIT), brief intraoperative exposure to heparin followed by an alternative anticoagulant as needed in the postoperative setting is recommended.

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