Suspicion of heparin-induced thrombocytopenia in internal medicine: How appropriate is the ordering of anti-PF4/heparin antibody testing?

Thrombocytopenia is frequent in hospitalized patients, and heparin-induced thrombocytopenia (HIT) is often suspected when a decrease in platelet count is concomitant with heparin treatment. ELISA tests used for anti-PF4/heparin antibodies detection usually have high sensitivity but only fair specificity for HIT. Pre-test probability scores (such as 4Ts or HEP scores) have been validated and a low probability score rules out HIT without anti-PF4/heparin testing. The aims of this study are to evaluate the appropriateness of anti-PF4/heparin testing according to pre-test probabilities of HIT and to compare the abilities of the 4Ts and HEP scores to avoid inappropriate anti-PF4/heparin testing. This retrospective observational study included 74 consecutive patients hospitalized in a general internal medicine division who had anti-PF4/heparin testing for suspicion of HIT. 4Ts and HEP scores were computed retrospectively. About 73% of patients who had ordering of an anti-PF4/heparin were at low risk according to the 4Ts score, and 46% according to the HEP score. Heparin was discontinued in 61% and 62% of low-risk patients according to 4Ts and HEP scores and switched to alternative anticoagulant in 31% and 32% of them, respectively. No case of HIT was diagnosed in patients with a low-risk score. One major bleeding and no thrombosis were observed. For the 4Ts score, the sensitivity was 100%, the negative predictive value (NPV) was 100%, the specificity was 77%, and the positive predictive value (PPV) was 20% (95% CI: 7–44). For the HEP score, the sensitivity was 100%, the NPV was 100%, the specificity was 49%, and the PPV was 10%. In conclusion, pre-test probability scores were vastly underused in this internal medicine population despite their ability to rule out HIT without laboratory testing in a large proportion of patients. Appropriate use of those instruments should be actively promoted.     

Heparin-induced thrombocytopenia: reducing misdiagnosis via collaboration between an inpatient anticoagulation pharmacy service and hospital reference laboratory

Misdiagnosis of heparin-induced thrombocytopenia (HIT) is common and exposes patients to high-risk therapies and potentially serious adverse events. The primary objective of this study was to evaluate the impact of collaboration between an inpatient pharmacy-driven anticoagulation management service (AMS) and hospital reference laboratory to reduce inappropriate HIT antibody testing via pharmacist intervention and use of the 4T pre-test probability score. Secondary objectives included clinical outcomes and cost-savings realized through reduced laboratory testing and decreased unnecessary treatment of HIT. This was a single center, pre-post, observational study. The hospital reference laboratory contacted the AMS when they received a blood sample for an enzyme-linked immunosorbent HIT antibody (HIT Ab). Trained pharmacists prospectively scored each HIT Ab ordered by using the 4T score with subsequent communication to physicians recommending for or against processing and reporting of lab results. Utilizing retrospective chart review and a database for all patients with a HIT Ab ordered during the study period, we compared the incidence of HIT Ab testing before and after implementation of the pharmacy-driven 4T score intervention. Our intervention significantly reduced the number of inappropriate HIT Ab tests processed (176 vs. 63, p < 0.0001), with no increase in thrombotic or hemorrhagic events. Overall incidence of suspected and confirmed HIT was <3 and <0.005 %, respectively. Overall cost savings were $75,754 (US) or 62 % per patient exposed to heparin between the pre and post intervention groups. Collaboration between inpatient pharmacy AMS and hospital reference laboratories can result in reduction of misdiagnosis of HIT and significant cost savings with similar safety.     

Egyptian experience of reliability of 4T's score in diagnosis of heparin induced thrombocytopenia syndrome

To evaluate the utility of the 4Ts clinical scoring system as a pretest probability method for detection of heparin-induced thrombocytopenia (HIT). Medical and surgical inpatients and outpatients at Kasr El Eini hospital. This single-centre series of 50 HIT testing referrals assessed combination of clinical score (thrombocytopenia, timing, thrombosis, other causes of thrombocytopenia not evident; 4T's), Heparin platelet factor 4 (H-PF4) rapid particle gel immunoassay (PaGIA) and 14C serotonin release assay (SRA) to develop a practical and well tolerated diagnostic strategy for HIT. Sixteen patients (32%) had a low 4T's score, 26 (52%) had an intermediate score and only eight (16%) had a high score. A positive H-PF4 by PaGIA was seen in seven patients (14%). As might be anticipated, the likelihood of obtaining a positive H-PF4 by PaGIA increased with an increasing clinical score, with positive H-PF4 by PaGIA results in low, intermediate and high scoring patients of 6.25, 7.7 and 50%, respectively. The positive predictive value of a positive PaGIA was 92%. The negative predictive value was 100%. Five patients (10%) in our cohort had a positive SRA. All patients with a positive SRA were included in the intermediate (two of 26 patients, 7.7%) or high (three of eight patients, 37.5%) score groups. The negative predictive value of a low 4T's score was 100%, effectively ruling out HIT. A low 4Ts score supports low probability of HIT based on the results of the PaGIA and SRA. Overall, the interrater reliability of the scoring system was fair.     

Timely diagnosis and management of heparin‐induced thrombocytopenia in a frequent request,low incidence single centre using clinical 4T’s score and particle gel immunoassay

Clinicians must promptly decide which patients suspected of having heparin‐induced thrombocytopenia (HIT) warrant a change in anticoagulation. This single‐centre series of 246 HIT testing referrals assessed the combination of clinical score (thrombocytopenia, timing, thrombosis, other causes of thrombocytopenia not evident; 4T’s), Diamed ID‐Heparin‐PF4 immunoassay (PaGIA) and 14C Serotonin Release Assay (SRA) to develop a practical and safe diagnostic strategy for HIT. A total of 142/256 (58%) referrals were in patients with a low 4T’s score, with 12/246 (5%) in the high scoring group. PaGIA was positive in 24/246 (9·7%) patients, whilst SRA was positive in 9/246 (3·6%). The overall positive predictive value of a positive PaGIA test alone was 37·5%, however this reached 80% for the high scoring group. Both negative PaGIA and low clinical score independently had negative predictive values of 100%. We subsequently developed an algorithm that, when applied to this cohort, would have resulted in 18/246 patients (7%) definitely requiring alternative anticoagulation, whilst a further 7/246 (2·8%) patients would have been considered on an individual basis. Ultimately (based on SRA) this would have resulted in 16/246 (6·5%) patients unnecessarily having a change in their anticoagulation, with 9/246 (3·6%) patients being ‘correctly treated’. The combination of 4T’s scoring and PaGIA permitted a practical and safe approach to rapid HIT diagnosis and management.     

Diagnosing heparin-induced thrombocytopenia: The need for accuracy and speed

Heparin-induced thrombocytopenia (HIT) is a prothrombotic condition resulting from pathogenic antibodies to complexes of heparin and platelet factor 4 (PF4). The diagnosis of HIT can be challenging due to the widespread use of heparin and the frequency of thrombocytopenia in hospitalized patients. Laboratory testing for HIT typically includes an immunoassay to detect antibodies to PF4-heparin and a functional assay. Current HIT diagnostic algorithms recommend using the 4Ts score to determine the need for HIT laboratory testing. Automated calculation of HIT clinical prediction scores in the electronic health record may improve the identification of patients who should undergo HIT testing. Another challenge in the management of patients with suspected HIT is the turnaround time of the laboratory testing needed to confirm the diagnosis. Due to the high daily thrombotic risk of HIT, clinicians must treat patients with intermediate to high pretest likelihood of HIT empirically while awaiting the test results. Treatment for HIT often involves alternative anticoagulants that lack reversal agents, which may increase bleeding risk, prolong hospital stays, and increase costs for patients suspected of having HIT. Rapid immunoassays hold promise to improve the speed of HIT diagnosis. These assays must retain a very high sensitivity for this “can't miss” diagnosis, yet have sufficient specificity to be of diagnostic value. A Bayesian approach has been proposed using two rapid immunoassays in succession, which decreased analytic turnaround time to 60 minutes. Such an approach has the potential to be a much-needed clinical advance in improving accuracy and speed in the diagnosis of HIT.     

Prospective evaluation of a rapid nanoparticle‐based lateral flow immunoassay (STic Expert® HIT) for the diagnosis of heparin‐induced thrombocytopenia

A rapid lateral flow immunoassay (LFIA) (STic Expert^® HIT), recently developed for the diagnosis of heparin‐induced thrombocytopenia (HIT), was evaluated in a prospective multicentre cohort of 334 consecutive patients. The risk of HIT was estimated by the 4Ts score as low, intermediate and high in 28·7%, 61·7% and 9·6% of patients, respectively. Definite HIT was diagnosed in 40 patients (12·0%) with positive results on both enzyme‐linked immunosorbent assay (Asserachrom^® HPIA IgG) and serotonin release assay. The inter‐reader reproducibility of results obtained was excellent (kappa ratio > 0·9). The negative predictive value of LFIA with plasma samples was 99·6% with a negative likelihood ratio (LR) of 0·03, and was comparable to those of the particle gel immunoassay (H/PF4‐PaGIA^®) performed in 124 cases. Positive predictive value and positive LR were 44·4% and 5·87, respectively, and the results were similar for serum samples. The probability of HIT in intermediate risk patients decreased from 11·2% to 0·4% when the LFIA result was negative and increased to 42·5% when it was positive. In conclusion, the STic Expert^® HIT combined with the 4Ts score is a reliable tool to rule out the diagnosis of HIT.     

Computerised risk scores to guide recognition and diagnosis in patients with possible heparin‐induced thrombocytopenia

The heparin‐induced thrombocytopenia computerised risk (HIT‐CR) score is designed to aid in the diagnosis of HIT. We sought to evaluate its potential clinical utility. In this retrospective cohort study, we collected HIT‐CR scores on all inpatients receiving heparin over a 4‐month period and performed chart reviews on the subset who independently underwent clinical diagnostic testing for HIT to identify patients with HIT. In all, 34 342 patients received heparin, 1744 had high‐risk HIT‐CR scores of ≥3 and 220 had the maximal risk score of 4. Only 6% of high‐risk and 10% of maximal‐risk patients underwent testing for HIT. Conversely, among all 317 patients who underwent independent testing for HIT, 67% had low‐risk HIT‐CR scores (<3). Among patients independently tested, the positive predictive value (PPV) was 6·6% [95% confidence interval (CI) 4·9–8·8%] and the negative predictive value (NPV) was 99·5% (95% CI 97·1–99·9%) at a HIT‐CR score cut‐off of 3, and the PPV was 22·7% (95% CI 12·7–37·4%) and NPV was 99·0% (95% CI 97·6–99·6%) at a cut‐off of 4. This study suggests clinicians fail to test most high‐risk patients and unnecessarily test many low‐risk patients for HIT. A reasonable approach to clinical application of HIT‐CR scores would be recommending no testing for patients with a score of <3 and recommend testing for patients with a score of 4.     

Prospective multicentre cohort study of heparin-induced thrombocytopenia in acute ischaemic stroke patients

Acute ischaemic stroke patients sometimes receive heparin for treatment and/or prophylaxis of thromboembolic complications. This study was designed to elucidate the incidence and clinical features of heparin-induced thrombocytopenia (HIT) in acute stroke patients treated with heparin. We conducted a prospective multicentre cohort study of 267 patients who were admitted to three stroke centres within 7 d after stroke onset. We examined clinical data until discharge and collected blood samples on days 1 and 14 of hospitalization to test anti-platelet factor 4/heparin antibodies (anti-PF4/H Abs) using an enzyme-linked immunosorbent assay (ELISA); platelet-activating antibodies were identified by serotonin-release assay (SRA). Patients with a 4Ts score ≥4 points, positive-ELISA, and positive-SRA were diagnosed as definite HIT. Heparin was administered to 172 patients (64·4%: heparin group). Anti-PF4/H Abs were detected by ELISA in 22 cases (12·8%) in the heparin group. Seven patients had 4Ts ≥ 4 points. Among them, three patients (1·7% overall) were also positive by both ELISA and SRA. National Institutes of Health Stroke Scale score on admission was high (range, 16-23) and in-hospital mortality was very high (66·7%) in definite HIT patients. In this study, the incidence of definite HIT in acute ischaemic stroke patients treated with heparin was 1·7% (95% confidence interval: 0·4-5·0). The clinical severity and outcome of definite HIT were unfavourable.     

La thrombopénie induite par héparine : mise au point

Heparin-induced thrombocytopenia (HIT) is a serious complication of heparin therapy. It is due to the synthesis of antibodies most often directed against platelet factor 4 (FP4) modified by heparin (H). HIT is manifested by a platelet count fall, associated with a high risk of venous or arterial thrombosis. The diagnosis of HIT is based on the assessment of clinical probability (4Ts score or change in platelet count after cardiac surgery) and the demonstration of heparin-modified anti-FP4 antibodies (FP4/H). If the immunological tests are positive, functional tests should be performed. In case of suspicion of HIT, it is necessary to urgently stop heparin therapy, to perform a doppler ultrasound of the lower limbs, and to prescribe an alternative anticoagulation agent at a curative dose. Currently, danaparoid sodium and argatroban are authorized. The diagnosis and management of HIT remain complex and requires multidisciplinary collaboration.     

Evaluating heparin-induced thrombocytopenia: the old and the new

Heparin-induced thrombocytopenia (HIT) is a rare but potentially serious complication of heparin use. Prompt diagnosis is crucial and requires the integration of clinical assessment and laboratory testing. Pretest clinical scoring systems (i.e., 4 Ts) have been established. Immunoassays can detect the presence of antibodies directed toward heparin-platelet factor 4 (H-PF4) complexes, but provide no information about their ability to activate platelets. A low clinical score, when combined with a negative immunoassay result obviates the need for further testing. However, immunoassays and 4 Ts scores have only modest specificity. Functional testing (serotonin release assay or heparin-induced platelet activation) remain important in confirming the presence of pathogenic H-PF4 antibodies, but are technically demanding to perform and limited in guiding clinical decisions in the acute setting. This review evaluates current immuno- and functional assays available in the laboratory diagnosis of HIT, and describes recent attempts to improve the specificity of enzyme immunoassays, including adopting an immunoglobulin G-specific assay and raising the optical density value cutoff for a positive result. The importance of donor selection and newer functional assays, including flow cytometry-based assays, are also discussed. A current approach to integrating clinical scoring, immunoassays, and functional testing for HIT is also outlined.     

Anticoagulation with recombinant hirudin and danaparoid sodium in pediatric patients

Patients receiving heparin are at risk of developing heparin-induced thrombocytopenia (HIT). Whereas in HIT I only reversible mild thrombocytopenia occurs within the first days of heparin treatment, HIT II may lead to potentially life-threatening thromboembolic events. Pediatric patients suffering from HIT II have been reported in a study on newborns and in a few reports on children and adolescents. However, thrombotic complications can be as severe in children as they are in adults. In the case of HIT II, the withdrawal of heparin is required and alternative anticoagulation should be started. In contrast to numerous investigations in adult patients, including prospective studies, experience with alternative anticoagulants in pediatric patients is limited. The available data were analyzed according to HIT II complications, alternative anticoagulation, and clinical outcome. In conclusion, HIT II represents a potentially dangerous complication of heparin therapy in pediatric patients also. Alternative anticoagulation applied in pediatric patients mainly included danaparoid sodium and recombinant hirudin. In most patients treated with these anticoagulants, effective anticoagulation and clinical improvement were observed. Because of limited experience, more data are required for optimal management of HIT II in young patients.     

Pitfalls in the diagnosis of heparin‐Induced thrombocytopenia: A 6‐year experience from a reference laboratory

Heparin‐induced thrombocytopenia (HIT) is caused by platelet‐activating antibodies against complexes of platelet factor 4 (PF4) and heparin. The diagnosis of HIT is contingent on accurate and timely laboratory testing. Recently, alternative anticoagulants for the treatment of HIT have been introduced along with algorithms for better HIT diagnosis. However, the increased reliance on immunoassays for the diagnosis of HIT may have harmful consequences due to the high rate of false positive results. To compare trends and implications of current HIT testing approaches, we analyzed results over a six‐year period from the McMaster University Platelet Immunology Reference Laboratory. From 2008 to 2013, 8,546 samples were investigated for HIT using both an in‐house IgG‐specific anti‐PF4/heparin enzyme immunoassay (EIA) and the serotonin‐release assay (SRA). Of 8,546 samples tested, 13.4% were true‐positives (positive in both assays); 65.6% were true‐negatives (negative in both assays); 20.9% were presumed false positive for HIT (EIA‐positive/SRA‐negative); and 0.2% were EIA‐negative/SRA‐positive. The frequency of EIA‐positive/SRA‐negative results increased over time (from 12.9% in 2008 to 22.9% in 2013). We found that the number of SRA‐negative samples was reduced from referring centers that used an immunoassay as an initial screen; however, 41% of those samples tested negative in the immunoassay and in the SRA at the reference laboratory. The suspicion of HIT continues at a high rate and the agreement between the EIA and SRA test results remains problematic. Am. J. Hematol. 90:629–633, 2015. © 2015 Wiley Periodicals, Inc.     

Platelet response to direct thrombin inhibitor or fondaparinux treatment in patients with suspected heparin-induced thrombocytopenia

Making a definitive diagnosis of heparin-induced thrombocytopenia (HIT) can be problematic. A prompt platelet rise following treatment has been proposed as a “post-test” criterion for diagnosis. However, the platelet response following discontinuation of heparin and initiation of a recommended alternative anticoagulant remains largely undefined and unstudied. This study aimed to characterize platelet response to initial treatment in patients with a low, intermediate, or high likelihood of having HIT. This was a multicenter retrospective cohort study. Patients were over 18 years in age, underwent serologic testing for HIT, and received alternative anticoagulation treatment for HIT. Classification of each patient’s likelihood of having HIT was based on an empiric, pre-hoc combination of the 4T score and serology results. The primary outcome for this study was a platelet count response after initiation of direct thrombin inhibitor (DTI) or fondaparinux therapy within 48 h. 124 patients were analyzed. The sensitivity and specificity of having an immediate platelet rise of at least 10,000/µL by day 2 after starting treatment among high-likelihood for HIT patients were 0.71 (95% CI 0.55–0.84) and 0.64 (95% CI 0.5–0.76), respectively. The negative predictive value of no platelet rise was 75.5% (95% CI 0.61–0.86). A prompt platelet count rise may be appropriate to consider along with other known criteria for the clinical diagnosis of HIT. The rise should be immediate following discontinuation of heparin and initiation of recommended treatment, with an upward rise within 48 h.     

Serial limited versus single complete compression ultrasonography for the diagnosis of lower extremity deep vein thrombosis

The diagnostic approach to deep vein thrombosis (DVT) has evolved during the last 3 decades. Contrast venography has been replaced by noninvasive tests. Compression ultrasonography (CUS) is currently the most widely used diagnostic test. Whereas CUS has a high accuracy for proximal DVT (thrombosis of the popliteal and more proximal veins), it has been shown to lack sensitivity and specificity for distal DVT. Ultrasonography can either be limited to the proximal veins and repeated within 1 week (serial limited CUS) or extended to both proximal and distal veins and performed on one occasion (single complete CUS). Both strategies are reliable diagnostic options for the management of patients with suspected DVT. The main limitation of proximal CUS is the need to repeat the test once in patients with initial negative findings. Conversely, complete CUS detects many distal DVTs for which systematic anticoagulation therapy is debatable and exposes patients to potentially unnecessary anticoagulation. Incorporation of D-dimer testing and clinical pretest probability assessment in the diagnostic algorithm is beneficial because it allows excluding DVT without the need for diagnostic imaging in about a third of patients.     

Is low serum albumin level a significant predictor for the development of heparin-induced thrombocytopenia-thrombosis?

The present study investigates the effect of albumin levels in patients who have developed heparin-induced thrombocytopenia (HIT) and heparin-induced thrombocytopenia-thrombosis (HITT). A retrospective observational cohort study was conducted at King Abudlaziz Medical City (KAMC), a university teaching hospital, on patients diagnosed with HIT between June 2013 and December 2014. Clinical and laboratory findings were used to confirm HIT. Albumin levels were reported on admission as baseline and during HIT occurrence. Twenty-eight patients were identified as HIT positive by enzyme-linked immunosorbent assay (ELISA), with a cutoff value of ≥1 optical density units and pretest probability “4Ts” score of ≥4. Of the 28 patients, nine (32%) developed HITT. Demographic characteristics of the patients who developed HIT and HITT were similar. The mean albumin level for patients who developed HITT was significantly lower than that for patients who developed HIT (p < 0.001). Our findings suggest that patients with low serum albumin levels are at greater risk of developing HITT. This finding awaits confirmation in larger prospective clinical trials.     

Utility of consecutive repeat HIT ELISA testing for heparin-induced thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is a serious complication of heparin therapy. Limited data are available regarding repeat HIT antibody testing after an initial negative test. We conducted a retrospective study to determine the utility of repeat testing. Heparin antibodies were detected using the GTI-PF4 enzyme-linked immunoabsorbent assay, ELISA (GTI Diagnostics, Waukesha, WI). Patients (n = 137) were assigned to one of three groups based upon the initial negative test optical density (OD) range of low = 0-0.132, medium = 0.133-0.267, and high = 0.268-0.399. A pretest clinical score was retrospectively determined using the "4T's" (Thrombocytopenia, Timing of platelet fall, Thrombosis, and the absence of oTher causes of thrombocytopenia). A subsequent positive ELISA was found in 16% (22/137) of patients who underwent repeat testing. Most of these patients had a low pretest clinical score (62%). Four patients had an interval change in the pretest score between the initial negative and subsequent positive tests. Only these four patients developed HIT with thrombosis (HITT). Eighty percent of patients with a high initial negative test OD value had a positive ELISA on repeat testing; however, the initial negative test OD value could not predict whether a patient developed HITT. In contrast, an increase in the pretest clinical probability between initial and repeat testing better predicted HITT. Consecutive repeat ELISA testing for heparin antibodies may be warranted in patients with an increase in their pretest clinical score after an initial negative test as an adjunct to confirm the diagnosis of HIT.     

The use of direct thrombin inhibitors in cardiovascular surgery in patients with heparin-induced thrombocytopenia

One of the most important adverse drug reactions that physicians encounter is the life- and limb-threatening prothrombotic syndrome known as heparin-induced thrombocytopenia (HIT). Unfractionated heparin (UFH), administered during cardiopulmonary bypass (CPB), is highly immunogenic. Heparin-dependent antibodies can develop in 25 to 50% of UFH-treated cardiac surgery patients within 5 to 10 days. These antibodies can activate platelets and are considered the causative agents of HIT. HIT is a relatively common complication, occurring in 1 to 3% of cardiovascular surgery patients when UFH administration is continued postoperatively. It is strongly associated with new thromboembolic events leading to limb amputation and death. In acute or recent (< 100 days) HIT, alternative anticoagulatory regimens are needed during CPB surgery for prevention of HIT-related thrombosis. Treatment options for such patients now generally include the use of alternative anticoagulants such as lepirudin, bivalirudin, or danaparoid, as well as a combined treatment with platelet-function inhibitors and heparin. In patients with a history of HIT and no detectable antibodies, heparin is currently the safest approach for high-dose anticoagulation during CPB. Before and after surgery, however, alternative anticoagulants should be used. The risk of clinical HIT after heart surgery could potentially be reduced by using low-molecular-weight heparins for postsurgery anticoagulation.     

Heparin-induced thrombocytopenia testing is over-utilized in cirrhosis & correlates with poor clinical outcomes

Introduction. Heparin-induced thrombocytopenia (HIT) is a serious complication seen in hospitalized, medically-ill patients. Evaluation for HIT using a commercially-available ELISA-based test has become increasingly common; however, it does have a high false positive rate. Implications of HIT testing in patients with cirrhosis have not yet been reported.Material and methods. We conducted a single-institution, retrospective review of all patients with cirrhosis admitted over a 29-month period. The student’s t-test and the χ² test were used for comparisons. We performed a stratified survival analysis using Kaplan-Meier and log rank testing.Results. A total of 1,305 patients had a HIT Ab sent during the study period. Of these patients, 106 had cirrhosis and were included in the study. Eighteen (17%) of the patients with cirrhosis were HIT Ab positive and four of the eighteen had a positive Serotonin Release Assay (SRA) confirmatory test. No difference was found in platelet nadir, thrombotic rate, length of stay, and patient survival between patients with positive HIT Ab and negative HIT Ab testing. No consistent treatment was used among patients who were HIT Ab positive, despite hematology service consultation. Patients who were HIT Ab negative were more likely to have undergone liver transplantation compared to those who were positive (27 vs. 5.5%, respectively; p = 0.048).Conclusion. Our data suggest that HIT Ab testing is over-used in patients with cirrhosis and is poorly predictive of outcomes. With a poor positive predictive value, HIT testing may add unnecessary complexity to an already complicated patient population.     

Risk for heparin-induced thrombocytopenia with unfractionated and low-molecular-weight heparin thromboprophylaxis: a meta-analysis

Heparin-induced thrombocytopenia (HIT) is an uncommon but potentially devastating complication of anticoagulation with unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH). Our objective was to determine and compare the incidences of HIT in surgical and medical patients receiving thromboprophylaxis with either UFH or LMWH. All relevant studies identified in the MEDLINE database (1984-2004), not limited by language, and from reference lists of key articles were evaluated. Randomized and nonrandomized controlled trials comparing prophylaxis with UFH and LMWH and measuring HIT or thrombocytopenia as outcomes were included. Two reviewers independently extracted data on thromboprophylaxis (type, dose, frequency, and duration), definition of thrombocytopenia, HIT assay, and rates of the following outcomes: HIT, thrombocytopenia, and thromboembolic events. HIT was defined as a decrease in platelets to less than 50% or to less than 100 x 10(9)/L and positive laboratory HIT assay. Fifteen studies (7287 patients) were eligible: 2 randomized controlled trials (RCTs) measuring HIT (1014 patients), 3 prospective studies (1464 patients) with nonrandomized comparison groups in which HIT was appropriately measured in both groups, and 10 RCTs (4809 patients) measuring thrombocytopenia but not HIT. Three analyses were performed using a random effects model and favored the use of LMWH: (1) RCTs measuring HIT showed an odds ratio (OR) of 0.10 (95% confidence interval [CI], 0.01-0.2; P = .03); (2) prospective studies measuring HIT showed an OR of 0.10 (95% CI, 0.03-0.33; P < .001); (3) all 15 studies measured thrombocytopenia. The OR was 0.47 (95% CI, 0.22-1.02; P = .06). The inverse variance-weighted average that determined the absolute risk for HIT with LMWH was 0.2%, and with UFH the risk was 2.6%. Most studies were of patients after orthopedic surgery.     

Heparin‐induced thrombocytopenia in myeloproliferative disorders: A rare or under‐diagnosed complication?

Patients with myeloproliferative disorders (MPD) are prone to develop thrombotic complications and thus frequently receive heparin. Surprisingly heparin-induced thrombocytopenia (HIT) has been rarely reported in MPD and is potentially under-diagnosed due to the relatively high platelet count. We report three patients with MPD who developed HIT; all presented with a relative fall of platelet counts (although without an absolute thrombocytopenia), thrombosis or skin necrosis and a positive test for HIT antibodies (particle gel immunoassay). Risk factors for developing HIT in our patients were exposure to unfractionated heparin, a recent surgical procedure and female gender. We review the literature on HIT in MPD and discuss the diagnosis of HIT in the absence of an absolute thrombocytopenia.