Pattern of Platelet Recovery in Predicting Outcome in Heparin-Induced Thrombocytopenia and Thrombosis.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4085-4085
Author(s):  
Indu Sabnani ◽  
Ajaz Khan ◽  
Patricia Tsang
Keyword(s):  
Platelet Count ◽  
Early Diagnosis ◽  
Liver Dysfunction ◽  
Patient Management ◽  
Response To Therapy ◽  
Cardiac Diseases ◽  
Platelet Factor ◽  
Platelet Recovery ◽  
Heparin Induced Thrombocytopenia ◽  
Recovery Group

Abstract Heparin-induced thrombocytopenia and thrombosis (HITT), a severe immune-mediated drug reaction, is often underdiagnosed. Early management of HITT with alternative anticoagulants can result in a favorable outcome. However, the morbidity and mortality associated with HITT remain high, posing challenges for patient management. We describe the clinical profile and pattern of platelet count recovery in a cohort of 34 patients diagnosed with HITT. This retrospective study consists of 164 patients screened for HITT over 18 months at our institution based on positive platelet factor 4 (PF4) IgG antibodies in the proper clinical setting. Patients who tested positive were divided on the basis of recovery of platelet count (increase to >100 × 109/L or by 1.5-fold by day 5 of diagnosis) into two groups: delayed and normal recovery. Of the 164 patients screened, 107 were admitted with cardiac diseases while 57 non-cardiac conditions. A total of 34 patients (21%) were tested positive for PF4 antibodies. Patients with underlying cardiac conditions were more likely to be diagnosed with HITT than non-cardiac patients (28% versus 7%, p=0.0012). The male to female ratio was 1:1.1, and the median age was 65 years. Nineteen of 34 patients (56%) had delayed platelet recovery, while the remaining 15 patients (44%) had normal platelet recovery by day 5. The mortality rate was 68% (13 of 19) in the delayed recovery group, compared to only 7% (1 of 15) in the normal recovery group (p=0.0004). Twelve of the 34 patients with liver dysfunction had delayed platelet recovery and died (figure 1). There were 6 venous and 5 arterial thrombotic episodes. A total of 13 patients (38%) were treated with Argatroban, a direct thrombin inhibitor (DTI) indicated for the treatment of HITT, but it did not seem to improve platelet recovery (Table 1). Eight of the 13 treated patients (62%) and 11 of the 21 untreated patients (52%) showed no platelet recovery by day 5. In conclusion, early diagnosis of HITT is critically important for patient management, and yet, diagnosis is often elusive due to a general lack of awareness of this condition. Underlying cardiac diseases appear to predispose patients to HITT, probably due to previous exposure and sensitization to heparin. Despite the availability of new anticoagulants, HITT remains an undertreated and highly fatal condition with overall mortality of 38% in our series. Underlying liver dysfunction appears to be associated with delayed platelet recovery and poor survival. Affect of DTI on platelet recovery needs to be further investigated. Optimal response to therapy requires early diagnosis and intervention. Further studies are necessary to enhance our understanding of this devastating condition to facilitate early diagnosis and proper treatment. Treatment and Survival of HITT Patients Outcome Treated with DTI Not treated Total Dead 6 7 13 Alive 7 14 21 Total 13 21 34 Pattern of Platelet Recovery in Patients with HITT with Delyaed Recovery > 5 days Pattern of Platelet Recovery in Patients with HITT with Delyaed Recovery > 5 days Pattern of Platelet Recovery in Patients with HITT with Delyaed Recovery < 5 days Pattern of Platelet Recovery in Patients with HITT with Delyaed Recovery < 5 days

Heparin-induced thrombocytopenia: when a low platelet count is a mandate for anticoagulation

Hematology ◽  
2009 ◽  
Vol 2009 (1) ◽  
pp. 225-232 ◽  
Author(s):  
Thomas L. Ortel
Keyword(s):  
Platelet Count ◽  
Heparin Therapy ◽  
Severe Thrombocytopenia ◽  
Drug Induced ◽  
Platelet Factor ◽  
Heparin Induced Thrombocytopenia ◽  
Immune Mediated ◽  
Number Of Patients ◽  
Increased Risk ◽  
Antibody Levels

Abstract Heparin-induced thrombocytopenia (HIT) is an immune-mediated disorder caused by the development of antibodies to platelet factor 4 (PF4) and heparin. The thrombocytopenia is typically moderate, with a median platelet count nadir of ~50 to 60 × 109 platelets/L. Severe thrombocytopenia has been described in patients with HIT, and in these patients antibody levels are high and severe clinical outcomes have been reported (eg, disseminated intravascular coagulation with microvascular thrombosis). The timing of the thrombocytopenia in relation to the initiation of heparin therapy is critically important, with the platelet count beginning to drop within 5 to 10 days of starting heparin. A more rapid drop in the platelet count can occur in patients who have been recently exposed to heparin (within the preceding 3 months), due to preformed anti-heparin/PF4 antibodies. A delayed form of HIT has also been described that develops within days or weeks after the heparin has been discontinued. In contrast to other drug-induced thrombocytopenias, HIT is characterized by an increased risk for thromboembolic complications, primarily venous thromboembolism. Heparin and all heparin-containing products should be discontinued and an alternative, non-heparin anticoagulant initiated. Alternative agents that have been used effectively in patients with HIT include lepirudin, argatroban, bivalirudin, and danaparoid, although the last agent is not available in North America. Fondaparinux has been used in a small number of patients with HIT and generally appears to be safe. Warfarin therapy should not be initiated until the platelet count has recovered and the patient is systemically anticoagulated, and vitamin K should be administered to patients receiving warfarin at the time of diagnosis of HIT.

scholarly journals Heparin-induced thrombocytopenia occurring after surgical treatment of atrial myxoma: A case report

2009 ◽  
Vol 137 (9-10) ◽  
pp. 540-544 ◽  
Author(s):  
Irena Djunic ◽  
Dragica Tomin ◽  
Nebojsa Antonijevic ◽  
Sinisa Gradinac ◽  
Mirjana Kovac ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Platelet Count ◽  
Correct Diagnosis ◽  
Corticosteroid Treatment ◽  
Clinical Score ◽  
Atrial Myxoma ◽  
Platelet Factor ◽  
Heparin Induced Thrombocytopenia ◽  
Unfractioned Heparin ◽  
Left Atrial Myxoma

Introduction Heparin-induced thrombocytopenia (HIT) is an acquired, prothrombotic disorder, caused by antibodies to a complex of heparin and platelet factor 4 (PF4) that activates platelets, resulting in the release of procoagulant microparticles, thrombocytopenia occurrence, generation of thrombin, and frequent thromboses. Case Outline We present a case of severe HIT in a 68-year-old female, which occurred after cardiosurgery of the left atrial myxoma with the aim to point out the importance of differential diagnosis of thrombocytopenia in patients recently exposed to heparin. Platelet count dropped on the eleventh postoperative day, six days after unfractioned heparin and enoxaparine treatment, to 4?109/l. The correct diagnosis failed to be made at first. Since thrombocytopenia remained refractory to a corticosteroid treatment and platelet transfusion, the patient was hospitalized on the 13th postoperative day at the Institute of Hematology. The diagnosis of HIT was confirmed with the high-probability clinical score (4T's) and strongly positive antiheparin-PF4 (PaGIA) test as well as positive platelet aggregation test. The treatment started with a smaller therapeutic doses of danaparoid than recommended of 750 U intravenous bolus and was followed by continuous infusions of 100 U per 1 h and intravenous gammaglobulins in full dosage for four days. The platelet count started to rise on the third day and it was completely normalized on the 5th day of the therapy. Conclusion Treatment of severe HIT with small doses of danaparoid supplemented by intravenous gamma globulin was successful. Additional awareness of heparin-induced thrombocytopenia is needed, especially of HIT in differential diagnosis of thrombocytopenia in patients recently exposed to heparin.

Comparison of Clinical Outcomes in Patients with Heparin-Induced Thrombocytopenia Treated with Direct Thrombin Inhibitors.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3942-3942 ◽  
Author(s):  
John L. Francis ◽  
Ranjeev Sandhu ◽  
Alane Drexler ◽  
John Dougherty
Keyword(s):  
Length Of Stay ◽  
Clinical Outcomes ◽  
Clinical Syndrome ◽  
Thrombin Inhibitors ◽  
Direct Thrombin Inhibitors ◽  
Efficacy And Safety ◽  
Platelet Factor ◽  
Platelet Recovery ◽  
Heparin Induced Thrombocytopenia ◽  
All Cause Mortality

Abstract Heparin-induced thrombocytopenia (HIT) is a clinical syndrome that has been reported to occur in 3–5% of patients treated with unfractionated heparin. If untreated, 36–50% of patients diagnosed with HIT develop life or limb-threatening thromboses. The occurrence of thrombosis, the most common serious complication of HIT, results in rates of amputation and death of 10–20% and 20–30% respectively. Thus, the desired clinical outcomes in patients with HIT are the prevention of thromboembolic complications, limb amputation, and death. The three direct thrombin inhibitors available in the U.S. are lepirudin, argatroban and bivalirudin. Lepirudin and argatroban have both been shown in clinical trials to significantly decrease the incidence of these complications in patients with HIT. Our institution also has experience with bivalirudin as treatment for HIT. We therefore sought to confirm whether all-cause mortality, length of stay, bleeding rate, time to platelet recovery, absolute change in platelet count following therapy, and percentage of therapeutic APTTs differed among patients treated with these agents at our institution. Data were collected by retrospective chart reviews, and from the Florida Hospital pharmacy computer system. Length of stay was calculated as the time to hospital discharge following the finding of a positive heparin-platelet factor 4 antibody test. For the purposes of comparison, the therapeutic range for APTT was taken as 50–90 seconds. As shown in the table, there were no statistically significant differences in any of the endpoints, when the efficacy and safety of the three direct thrombin inhibitors were compared. It therefore appears that within our institution, each of the direct thrombin inhibitors are equally efficacious and safe in treating the clinical syndrome of HIT, with similar outcomes with respect to length of stay, recovery of platelet counts, incidence of bleeding, and overall mortality. We conclude that selection of a direct thrombin inhibitor can be guided by the patient’s clinical status and organ function instead of efficacy and safety considerations. Drug n All-cause mortality (%) Length of stay (days) Bleeding (%) Time to platelet recovery (days) Therapeutic APTT (%) Lepirudin 7 28.5 11.0 28.5 5.3 70 Argatroban 20 30.0 15.1 20.0 5.2 65 Bivalirudin 24 25.0 18.7 25.0 5.4 74 P-value NS NS NS NS NS

Platelet Factor 4 Regulates Platelet Count In Vivo: Implications for Platelet Recovery after Cytotoxic Therapy.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3144-3144
Author(s):  
Michele P. Lambert ◽  
M. Anna Kowalska ◽  
Mortimer Poncz
Keyword(s):  
Bone Marrow ◽  
Platelet Count ◽  
Mononuclear Cells ◽  
Physiological Role ◽  
Platelet Factor 4 ◽  
Cytotoxic Therapy ◽  
Platelet Factor ◽  
Platelet Recovery ◽  
Platelet Counts

Abstract Platelet factor 4 (PF4), a platelet-specific CXC chemokine, was the first reported negative autocrine regulator of megakaryopoiesis in vitro. To define the physiological role(s) of PF4, we established mice that either were deficient in murine (m) PF4 (mPF4−/−) or that over-expressed human (h) PF4 (hPF4+/+). These mice had a level of PF4 ~6-fold greater than that present in human platelet controls. All lines studied had been backcrossed onto a C57Bl/6J background for >10 generations. Platelet counts in these animals correlated inversely with PF4 determined expression, beginning with a low platelet count of 702 ± 57 x 103/μL in the hPF4+/+ mice < hPF4+ < wildtype (WT) < mPF4+/− < mPF4−/− mice in which the platelet count was 1,404 ± 117 x 103/μL. The half-life of the platelets from the hPF4+/+ was identical to that of WT mice. Cultured bone marrow mononuclear cells (BMMNC) in serum-free media showed that each line had identical efficiency in growing megakaryocyte colonies, suggesting that megakaryocyte progenitor cells in these different genetic lines were intrinsically normal. Megakaryocyte colony numbers derived from WT BMMNC were reduced by the addition of recombinant PF4 or supernatant from irradiated bone marrow of hPF4+ mice, but not from mPF4−/− mice, suggesting that megakaryocyte lysis in vivo during cytoreductive therapy may contribute to the subsequent thrombocytopenia by releasing PF4. Additionally, a rabbit polyclonal anti-mPF4 antibody (Ab) was able in culture to significantly reverse this inhibitory effect of PF4 on megakaryopoiesis. Preliminary cytoreductive studies using either 600 cGy or 150 mg/kg of 5-fluorouracil (5-FU) intraperitoneally (IP) were performed. In irradiation studies, mPF4−/− mice began to recover on the same day as WT littermates, but they clearly had higher platelet counts at their nadir, with a drop to only 42 ± 7% of baseline vs. 32 ± 6% in the WT mice (n =12 in each arm, p = 0.06). By Day 13, 9 of 12 mPF4−/− mice had recovered to >75% of baseline, while only 3 of 12 WT mice had recovered (p <0.001). hPF4+ mice (n = 7) were studied after 5-FU treatment. Compared to WT littermates (n = 9), the hPF4+ recovered later (15.6 ± 2.2 vs. 11.2 ± 1.5 days, p < 0.0003), and clearly had significantly greater drop to 30 ± 6% vs. 56 ± 9% of baseline (p < 0.00001). By day 15, all of the WT mice had recovered, but only 43% of hPF4+ mice had returned to >75% of baseline platelet count (p = 0.009). To examine if anti-mPF4 Ab was protective of cytotoxic therapy-induced thrombocytopenia, WT mice were treated with 180 mg/kg of 5-FU and were given either anti-mPF4 Ab (25 mg/kg, IV, x 2) or an equal volume of vehicle. By day 5, the Ab-treated group had a platelet count of 45 ± 6% vs. 32 ± 4% in the untreated (n > 13 per arm, p = 0.015). Platelet counts remained higher in the Ab-treated arm throughout the study. By day 10 after intervention, 9 of 16 mice of the Ab-treated arm had platelet counts over 75% of the baseline, while only 3 of 13 control mice did (p < 0.001). Thus, it appears that PF4 is an important negative autocrine regulator of platelet count in vivo. Excessive release of PF4 following cytotoxic therapy may be a mediator of treatment-related thrombocytopenia. Strategies directed to alleviate the consequence of released PF4 may have clinical benefit in ameliorating this thrombocytopenia.

The Incidence of Thrombosis in Patients with Isolated Heparin Induced Thrombocytopenia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1049-1049 ◽  
Author(s):  
Rachel P. Rosovsky ◽  
Omar I. Abdel-Wahad ◽  
Elizabeth M. Van Cott ◽  
David J. Kuter
Keyword(s):  
Platelet Count ◽  
Mortality Rate ◽  
Massachusetts General Hospital ◽  
Thrombotic Event ◽  
Radiographic Examination ◽  
Platelet Factor ◽  
Heparin Induced Thrombocytopenia ◽  
Total Incidence ◽  
Objective Evidence ◽  
Heparin Exposure

Abstract Introduction: Heparin-induced thrombocytopenia type-II (HIT) is a serious prothrombotic disorder caused by heparin exposure. The incidence of thrombosis in patients with isolated HIT, defined as HIT without clinically evident thrombosis at the time of diagnosis, is not well established. Aim: The purpose of this prospective study was to determine the total incidence of thrombotic events after diagnosis of isolated HIT from radiographic evidence of asymptomatic deep venous thrombosis (DVT) plus radiographic confirmation of symptomatic thrombosis. Patients and Methods: We evaluated all patients with a positive enzyme-linked immunoassay (ELISA) for heparin-platelet factor 4 (PF4) antibody (Ab) daily at Massachusetts General Hospital from 10/10/05 to 5/13/06. Inpatients with (1) a positive PF4 Ab test, (2) thrombocytopenia, as defined by a ≥50% drop from baseline platelet count and/or a fall in platelet count to <150×109/L, in association with heparin exposure, (3) no signs or symptoms of thrombosis at time of the positive Ab test, and (4) no other definitive etiology of thrombocytopenia were considered to have isolated HIT and included for study. Patients with a prior diagnosis of HIT, DVT, pulmonary embolism, or peripheral arterial thrombosis were excluded. Within 72 hours of diagnosis and of initiation of a non-heparin anticoagulant, all included patients underwent radiographic examination for asymptomatic DVT in the lower extremities (LE). Objective evidence of thrombotic events other than LE DVT after the diagnosis was also recorded. Daily platelet count, type and timing of all anticoagulants, use of blood products, and PF4 Ab titer were collected to determine if there was an association between these factors and development of thrombosis. Mortality rate during hospitalization was also recorded. Results: Of the 158 patients with a positive heparin-PF4 Ab, 64 patients met criteria for study, 14 of which were lost to follow-up. Among the 50 remaining eligible patients, the total incidence of thrombosis was 20% (12% were found to have an asymptomatic thrombotic event and 8% developed a symptomatic thrombotic event). Development of thrombosis was independently associated with platelet transfusion (p=0.005) and with the degree of platelet count nadir as expressed by platelet count (p=0.038) or by percent decrease from baseline (p=0.031). There was no association between the PF4 Ab titer or the type and timing of non-heparin anticoagulant and development of thrombosis. The overall mortality rate in patients diagnosed with isolated HIT during hospitalization was 22%. Conclusion: The total incidence of thrombotic events in isolated HIT was 20%, with greater than half of the events being asymptomatic thromboses found only by radiographic examination. This high incidence of asymptomatic LE DVT suggests that routine investigation for LE DVT should be performed in this patient population and that patients with isolated HIT should be treated with a non-heparin anticoagulant. Our findings also confirm the current recommendation to avoid platelet transfusions in patients with isolated HIT as we found an increased rate of thrombosis associated with this practice.

scholarly journals Spontaneous Heparin-Induced Thrombocytopenia and COVID-19 Infection

Blood ◽  
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.

Antibodies to Macromolecular Platelet Factor 4-Heparin Complexes in Heparin-induced Thrombocytopenia: a Study of 44 Cases

1995 ◽  
Vol 73 (01) ◽  
pp. 021-028 ◽  
Author(s):  
J Amiral ◽  
F Bridey ◽  
M Wolf ◽  
C Boyer-Neumann ◽  
E Fressinaud ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Platelet Aggregation ◽  
Early Diagnosis ◽  
Healthy Subjects ◽  
Platelet Factor 4 ◽  
Platelet Factor ◽  
Heparin Induced Thrombocytopenia ◽  
Sulphated Polysaccharides ◽  
Major Interest ◽  
Heparin Complexes

SummaryAs heparin-PF4 (H-PF4) complexes are the target for antibodies associated to heparin-induced thrombocytopenia (HIT), an ELISA has been developed and optimised for testing antibodies binding to H-PF4. This test was consistently negative in 50 healthy subjects (A492 <0.3) and 35 patients with other causes of thrombocytopenia (A492 <0.5). In contrast, 43 out of 44 HIT patients showed antibodies to H-PF4 (A492 = 1.70 ± 0.81) including 5 patients with a negative platelet aggregation test. In one patient with HIT, antibodies to H-PF4 were already present at day 7, whereas platelet counts dropped ≤ 100 × 109/l only at days 11–12. Surprisingly, among 41 patients under heparin for >7 days, 5 showed antibodies to H-PF4, without HIT. These findings underline the major interest of this ELISA for the early diagnosis of HIT. We also showed that LMWH as well as other sulphated polysaccharides can bind to HIT antibodies in the presence of PF4 and that their reactivity is dependent on the molecular weight and the sulphation grade. The mechanism for HIT involves platelet PF4 receptors which bind the macromolecular H-PF4 complexes formed in the presence of a well defined heparin/PF4 ratio.

EFFECT OF A SYNTHETIC ANTICOAGULANT (MD 805) ON PLATELETS IN HUMAN VOLUNTEERS AND HEMODIALYSIS PATIENTS.

1987 ◽  
Author(s):  
T Matsuo ◽  
T Yamada ◽  
K Nakao
Keyword(s):  
Platelet Count ◽  
Thrombus Formation ◽  
Normal Subjects ◽  
Hemodialysis Patients ◽  
Normal Range ◽  
Synthetic Compound ◽  
Platelet Factor ◽  
Heparin Induced Thrombocytopenia ◽  
Human Volunteers ◽  
Platelet Release

Twelve normal subjects were injected with 5000 U of commercial mucous heparin with or without preloading of 1.0 g aspirin, and 0.2 mg/kg MD 805, an arginine derivative, which is a new synthetic compound with an extremely strong affinity for thrombin, at an interval of 4 weeks after each injection. Heparin injection with or without aspirin significantly increased platelet factor 4 release. In contrast, the preloading of aspirin significantly inhibited the decrease of platelet count and the elevation of /8 thromboglobulin induced by heparin. However, MD 805 had no effect on platelet release proteins, and adequate anticoagulation by APTT was still present 60 min after the injection. MD 805 shows no stimulative effects on platelets such as with heparin.In the case of the patient's study, three patients complicated with heparin induced thrombocytopenia plus thrombus formation in the extracorporeal circulation during hemodialysis, and were treated with MD 805 instead of heparin. The platelet counts in those patients quickly returned to within the normal range, and adequate anticoagulation was obtained in the following hemodialysis sessions and no further bleeding or clot formation was noted.In conclusion, MD 805 may represent a useful alternative anticoagulant in patients with heparin induced thrombocytopenia.

Comparison of Antigen and Activation Assays with a Probability Scoring Model for the Diagnosis of Heparin Induced Thrombocytopenia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3215-3215
Author(s):  
Dimitrios Scarvelis ◽  
Gail Rock
Keyword(s):  
Laboratory Testing ◽  
Laboratory Tests ◽  
Serotonin Release ◽  
Reference Standard ◽  
Platelet Response ◽  
Platelet Factor ◽  
Platelet Recovery ◽  
Heparin Induced Thrombocytopenia ◽  
Activation Assay ◽  
Heparin Anticoagulation

Background: Heparin induced thrombocytopenia (HIT) is a syndrome characterized by thrombocytopenia and an elevated risk of thrombosis. In the evaluation of patients with suspected HIT, laboratory testing is used to help differentiate between those patients who have HIT and those who do not and therefore do not require non-heparin anticoagulation. Laboratory tests include activation (serotonin release, heparin-induced platelet aggregation, ATP luminescence) and antigen (enzyme-linked immunoabsorbant assay (ELISA)) assays directed against the platelet factor 4-heparin or PF4/PVS complex. A pre-test scoring system (Warkentin 4T’s) has been derived to assess the probability of HIT which can be used in conjunction with laboratory testing in the evaluation for HIT. Objectives: To compare the activation assay used at The Ottawa Hospital (ATP luminescence) with the PF4 enhanced® ELISA and correlate results with clinical data. Methods: Patients undergoing HIT testing were identified. ELISA and activation assays were performed. Charts were reviewed in order to derive a 4T’s score and to assess response to therapeutic non-heparin anticoagulation (when administered). Correlation between ELISA, activation assay, 4T’s score and platelet response to alternative anticoagulation was determined. Sensitivity, specificity, PPV and NPV of laboratory tests or 4T’s scores were calculated depending on the measure chosen as the reference standard to diagnose HIT. Results: 111 patients undergoing HIT testing were evaluated. 41 and 43 were positive by ELISA (OD > 0.4) or activation assay respectively. 12 were positive only by ELISA (mean optical density (OD): 1.27) and 10 were positive by both activation assay and ELISA (mean OD: 2.28). Clinical information was available for 70 patients. 26 of these received therapeutic non-heparin anticoagulation as treatment for suspected HIT. Reference standard= activation assay: ELISA: Sens 95% (95% CI 73–99%), Spec 80% (66–89%), PPV 66% (46–81%), NPV 98% (86–100%). 4T’s (low vs. high score): Sens 85% (54–97%), Spec 95% (83–99%), PPV 85% (54–97%), NPV 95% (83–99%). ELISA OD > 1.5 + high 4T’s score: Sens 61% (36–82%), Spec 100% (56–100%), PPV 100% (68–100%), NPV 50% (24–76%). Reference standard= 4T’s score (high and low score only, excludes intermediate category): ELISA: Sens 85% (53–97%), Spec 77% (61–88%), PPV 52% (30–74%), NPV 94% (79–99%). Activation: Sens 85% (54–97%), Spec 95% (83–99%), PPV 85% (54–97%), NPV 95% (83–99%). Reference standard= “clear response to non-heparin anticoagulation” defined as significant platelet increase within 48 hours of start of therapy and no other explanation for platelet recovery: ELISA: Sens 100% (72–100%), Spec 54% (26–80%), PPV 68% (43–86%), NPV 100% (56–100%). Activation: Sens 85% (54–97%), Spec 69% (39–90%), PPV 73% (45–91%), NPV 82% (48–97%). 4T’s (low vs. high score): Sens 90% (54–99%), Spec 100% (60–100%), PPV 100% (63–100%), NPV 89% (51–99%). ELISA OD > 1.5 + 4T’s (low vs. high score): Sens 89% (51–99%), Spec 100% (56–100%), PPV 100% (60–100%), NPV 88% (47–99%). Conclusions: A high 4T’s score best predicts a clinical response to non-heparin therapeutic anticoagulation when HIT is suspected. ELISA OD > 1.5 does not add additional information in this respect. A negative ELISA and a low 4T’s score have comparable NPVs when an activation assay is the reference standard. Future trials should employ a clinical reference standard such as “clear response to non-heparin anticoagulation” when evaluating the operator characteristics of HIT assays.

Spontaneous Heparin-Induced Thrombocytopenia Syndrome: Two New Cases and a Proposal For Defining This Disorder

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2328-2328 ◽  
Author(s):  
Theodore E. Warkentin ◽  
Paul Andrew Basciano ◽  
Richard A. Bernstein
Keyword(s):  
Platelet Count ◽  
Platelet Activation ◽  
Research Funding ◽  
Left Vertebral Artery ◽  
Platelet Factor ◽  
Shoulder Hemiarthroplasty ◽  
Heparin Induced Thrombocytopenia ◽  
Activation Assay ◽  
Count Recovery ◽  
Heparin Exposure

Abstract Introduction Heparin-induced thrombocytopenia (HIT) is a transient, autoimmune-like, prothrombotic disorder caused by heparin-dependent, platelet-activating IgG reactive against platelet factor 4/heparin (PF4/H). There is an emerging literature (Am J Med 2008;121:632-6. J Thromb Haemost 2008;6:1598-1600; Thromb Haemost 2013;109:669-75) pointing to rare instances of “spontaneous” HIT in patients without preceding heparin. We report 2 new cases and propose a definition for this controversial disorder. CASE #1. A 62-y.o. man presented with left middle cerebral artery stroke and thrombocytopenia (platelet count, 65×109/L). There was no previous history of thrombocytopenia, surgery, hospitalization, or heparin exposure. Clot extraction performed with heparin was complicated by further platelet count decline to 27 (nadir) and progressive thrombosis of the carotid artery. Aspirin was started, and the platelets recovered to >150 by day 13. CASE #2. A 54-y.o. female developed right leg swelling, left-upper extremity weakness/paresthesias, and thrombocytopenia (61×109/L) 15 days post-shoulder hemiarthroplasty; no intra-/postoperative heparin had been given. Brain MRI demonstrated acute infarct in the left posterior inferior cerebellar artery territory; angiography showed non-visualization of the left vertebral artery. Ultrasound revealed right lower-limb deep-vein thrombosis. Heparin treatment resulted in further platelet count fall to 37 (nadir). Treatment with argatroban, followed by fondaparinux, was associated with platelet count recovery to >150 by day 39. Methods Testing for HIT antibodies was performed by commercial EIA-IgG/A/M (Immucor GTI Diagnostics), in-house EIA-IgG (McMaster), and serotonin-release assay (SRA). Results Both patients’ sera (obtained before any heparin administration) tested strongly positive for HIT antibodies (Table), including strong platelet activation at 0.1 and 0.3 IU/mL heparin, as well as at 0 U/mL heparin, with no platelet activation at 100 IU/mL heparin: these serological features are characteristic of “delayed-onset HIT” (Ann Intern Med 2001;135:502-6). Antibody reactivity declined markedly by 2 to 4 weeks (including loss of platelet-activating properties at 0 IU/mL heparin), in keeping with the usual transience of HIT antibodies (N Engl J Med 2001;344:1286-92), and paralleling both patients’ platelet count recovery. Discussion These cases further support spontaneous HIT as an unusual explanation for acute arterial stroke and thrombocytopenia. One patient had preceding orthopedic surgery, an event previously reported with spontaneous HIT (Thromb Haemost 2013;109:669-75). The strong serum-dependent platelet activation at 0 IU/mL heparin helps to explain how thrombocytopenia and thrombosis can occur in a patient not receiving heparin. RECOMMENDATION. Based on the serological findings of these and previous cases, we propose that a definitive diagnosis of spontaneous HIT syndrome should be based upon all of the following criteria: thrombocytopenia, thrombosis, lack of proximate heparin exposure, strong-positive PF4-dependent immunoassay(s), and a strong-positive platelet activation assay featuring both heparin-dependent (e.g., high heparin neutralization) and heparin-independent platelet activation (at 0 IU/mL heparin). Disclosures: Warkentin: Pfizer Canada: Honoraria; Paringenix: Consultancy; Immucor GTI Diagnostics: Research Funding; WL Gore: Consultancy; GSK: Research Funding.

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