Thrombocytopenia Is More Common and Nadir Occurs Earlier with Unfractionated Heparin Than with Low Molecular Weight Heparin - Results from the Prospective Catch Registry.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2197-2197
Author(s):  
Stephan Moll ◽  
Charles S. Abrams ◽  
Lawrence Rice ◽  
Richard C. Becker ◽  
Peter B. Berger ◽  
...  

Abstract Background : Thrombocytopenia in the patient on heparin can have various etiologies, including benign reversible causes and serious, potentially life-threatening ones, such as heparin induced thrombocytopenia (HIT). Knowledge about the prevalence of and timecourse of thrombocytopenia in heparin-treated patients may be helpful to develop systems of alerting clinicians to possible HIT and determining how frequently to check blood counts to detect thrombocytopenia that may be heralding HIT. Methods : The CATCH registry is a prospective registry of inpatients enrolled between March 2003 and April 2004 at over 50 US hospitals in 3 strata: [1] receiving > 96 hours of unfractionated heparin (UFH) or low molecular weight heparin (LMWH), [2] developing thrombocytopenia (platelets >50% reduction from baseline or <150,000/mm3) in the cardiac care unit and [3] patients on whom HIT tests were ordered. Here we present the data of the prolonged heparin stratum. Results : 1,121 and 861 patients received UFH and LMWH, respectively, for > 96 hours. A platelet count decrease of > 50 % from baseline was seen more frequently in patients on UFH than in patients on LMWH (10.7% and 7.9 %, respectively; p = 0.03). The parameters that predicted development of thrombocytopenia in the UHF group were length of heparin therapy, body mass index, and admission to a cardiac service; the only parameter predicting thrombocytopenia in the LMWH group was length of LMWH treatment. Of the patients with decreased platelet count by > 50 % from baseline (for UFH n = 120; for LMWH n = 68), this drop occurred in the UFH group at a median of 3.0 days after initiation of heparin and at a median of 4.0 days in the LMWH group. The difference in timing between the 2 groups was not statistically significant (p = 0.205). The platelet nadir was reached after a median /mean of 4.0 / 7.4 days in the UFH group, and 8.0 / 11.4 days in the LMWH group. This was statistically significantly different between the 2 groups (p-value = 0.0025). Conclusions : A platelet count decrease of > 50 % from baseline occurs frequently in inpatients treated with prolonged heparin. It occurs slightly more frequently on UFH than on LMWH. The median time to onset of thrombocytopenia (> 50 % decrease from baseline) occurs early, at 3–4 days. Daily platelet count checks in the first few days of heparin therapy may be helpful to rapidly discover thrombocytopenia that may then prompt HIT testing.

1998 ◽  
Vol 4 (2) ◽  
pp. 126-128 ◽  
Author(s):  
Bruno Girolami ◽  
Paolo Prandoni ◽  
Laura Rossi ◽  
Antonio Girolami

The purpose of this study was to evaluate the in cidence of transaminase elevation in patients treated with un fractionated (UFH) or low molecular weight heparin (LMWH). Patients receiving UFH, nadroparin, or reviparin for venous thromboembolism and with normal baseline transaminase val ues were evaluated for serum transaminase levels 10-14 days after the start of heparin therapy or at the end of treatment. The incidence of high transaminase was 4.7% overall (95% CI, 2.2 to 7.3), while it was 2.9% (95% CI, 0.1 to 5.6) and 6.7% (95% CI, 2.5 to 11.0) with UFH and LMWH treated patients, respec tively. The difference was equal to -3.8% (95% CI, -8.9 to 1.2) and the common odds ratio was equal to 0.38 (95% CI, 0.12 to 1.16, p = .09). Nadroparin treated patients showed a 5.7% (95% CI, 1.3 to 10.2) incidence of high transaminase levels, while reviparin treated patients presented a 10.3% incidence (95% CI, -0.7 to 21.4). The comparison with UFH showed a mild trend in favor of UFH when compared with nadroparin, but not with reviparin. In conclusion, the incidence of trans aminase increase during heparin treatment for a venous throm boembolic event is equal to 3%, 6%, and 10% in UFH-, na droparin-, and reviparin-treated patients, respectively. LMWHs showed a slightly higher average incidences of hypertransami nasemia as compared with UFH. Differences did not reach statistical significance. Key Words: Unfractionated heparin— Low molecular weight heparin—Hypertransaminasemia.


1992 ◽  
Vol 68 (01) ◽  
pp. 014-018 ◽  
Author(s):  
S Lopaciuk ◽  
A J Meissner ◽  
S Filipecki ◽  
K Zawilska ◽  
J Sowier ◽  
...  

SummaryIn a prospective multicenter trial, 149 consecutive patients with phlebographically proven proximal and/or distal deep vein thrombosis of the leg were randomly allocated to receive subcutaneously for 10 days either low molecular weight heparin CY 216 (Fraxiparine) in a fixed dose or unfractionated heparin (UFH) in doses adjusted according to the activated partial thromboplastin time. Pre- and post-treatment phlebograms were assessed blindly using the Arnesen’s score system in 134 patients available for analysis of the treatment efficacy. The mean phlebographic score after 10 days of treatment was significantly decreased in both groups (p <0.001) in comparison with the baseline score but the difference in score changes between the two groups was not statistically significant. There was an improvement in 45/ 68 patients (66%) in the Fraxiparine group and in 32/66 patients (48%) in the UFH group, and an increase in the thrombus size in 10/68 (15%) and 12/66 (18%), respectively. One symptomatic non-fatal pulmonary embolism and one major bleeding episode were observed in the UFH group. During a follow-up period of 3 months, two rethromboses had occurred in the UFH group and none in the Fraxiparine group. It is concluded that subcutaneous fixed dose Fraxiparine is safe and at least as effective as subcutaneous adjusted UFH in the treatment of deep vein thrombosis.


Author(s):  
Gunduz T ◽  
Cakir M ◽  
Bakirci EM ◽  
DEGIRMENCI H

Heparin-İnduced Thrombocytopenia (HIT) is a life-threatening complication that occurs in a small percentage of exposed patients (e.g. unfractionated heparin, Low Molecular Weight Heparin [LMWH]) regardless of dose and treatment management.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1282-1282
Author(s):  
Maarten ten Berg ◽  
Patricia Van den Bemt ◽  
Albert huisman ◽  
Fred Schobben ◽  
Toine Egberts ◽  
...  

Abstract Laboratory monitoring for early detection of adverse drug reactions is recommended for many drugs. For patients treated with low molecular weight heparin (LMWH), the Summary of Product Characteristics (SPC) and clinical guidelines recommend to monitor the platelet count for heparin-induced thrombocytopenia (HIT), a potentially life-threatening adverse event, characterised by a typical drop in platelet count. When the platelet count drops without obvious explanation in these patients, testing for heparin-platelet factor 4 antibodies (HPF4-Ab) and initiating alternative anticoagulation are advised. In the current study adherence to recommended platelet count monitoring in clinical patients without thrombocytopenia-associated diseases treated with LMWH for at least five days at our institution, and adherence to recommended testing for HPF4-Ab and initiation of alternative anticoagulation in patients with potential HIT (defined as a drop of at least 50% in platelet count between days 5 and 14 following the start of LMWH treatment, or stopdate, whichever occurred first, compared to the highest platelet count within days 1–4) were investigated. Data from the Utrecht Patient Oriented Database (UPOD) were used for this retrospective cohort study. Inpatients exposed to the LMWHs dalteparin or nadroparin for at least five days during the period 2004–2005 were included. Patients with thrombocytopenia-related diseases were excluded. Firstly, adherence to recommended platelet count monitoring, based on recommendations from SPCs and clinical guidelines, was investigated. Secondly, the association between patient- and treatment characteristics and obtaining at least 2 platelets counts during treatment was investigated. Thirdly, adherence to recommended testing for HPF4-Ab and initiating treatment with danaparoid was investigated in patients with potential HIT. 6,804 patients with 7,770 episodes of LMWH treatment of at least five days were included. Adherence to the recommendations for platelet count monitoring from the SPC of nadroparin and dalteparin was 36.5% and 26.3% respectively. Adherence to the different platelet count monitoring recommendations from the 2002 clinical guideline on HIT was 23.0% and 41.5%. Obtaining at least 2 platelet counts during treatment was found to be strongly associated with ICU admission, previous UFH exposure, and a treatment duration of at least 10 days. There were 98 patients with potential HIT. Adherence to testing for HPF4-Ab in patients with potential HIT was 6.1%. Adherence to starting alternative anticoagulation in patients with potential HIT treatment was 0%. The results of this study suggest that adherence to recommendations for monitoring for HIT with LMWH is low at our institution. The results of this study justify to say that there is a need to think of appropriate actions for improving the awareness of HIT as an adverse reaction to LMWH, and to secure the safe use of LMWH.


2005 ◽  
Vol 71 (2) ◽  
pp. 132-134
Author(s):  
Robert L. Weinsheimer ◽  
Edward Libby ◽  
Thomas R. Howdieshell

We present a patient with chronic renal insufficiency who developed a massive posttraumatic abdominal wall hematoma after a single therapeutic dose of enoxaparin administered during workup of chest pain. Surgical evacuation of the hematoma was required to control life-threatening hemorrhage. Low-molecular-weight heparin use is not without risk and mandates appropriate indication and accurate dosing. Bleeding can occur at any site during heparin therapy, and abdominal wall hematoma should be considered as a source after traumatic injury.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4064-4064
Author(s):  
David L. McGlasson ◽  
Daniel A. Kaczor ◽  
Richard A. Krasuski ◽  
Charles L. Campbell ◽  
Maria R. Kostur ◽  
...  

Abstract Introduction: The purpose of this study was to determine if the anti-FXa (FXa)assay is less affected by pre-analytical variables in monitoring patients on unfractionated heparin (UFH) and low molecular weight heparin (LMWH) than the activated partial thromboplastin time (APTT). Methods: Twenty-six subjects receiving enoxaparin (LMWH) in varying concentrations were randomly selected and consented for this study. Twenty individuals receiving UFH were also randomly selected and consented. Each study subject had 6 tubes of citrated blood obtained by venipuncture in a one-time blood draw. Two vacutainer tubes were 3.8% sodium citrate, two were 3.2% sodium citrate, and two had an anticoagulant called CTAD. All of the tubes were from Becton-Dickinson, Inc. One tube from each set had a blood to anticoagulant ratio of 9:1. The other tube had an intentional “short-draw” of approximately 6:1 blood to anticoagulant ratio. All six specimens on each subject had an APTT and a FXa assay corresponding to the type of heparin they were receiving performed by a kit from Diagnostica-Stago, Inc., called STA-Rotachrom Heparin Assay. All tests were performed on an STA-R automated coagulation analyzer. Each FXa heparin assay was performed using either a standard UFH or LMWH calibration curve and a HYBRID curve using a specific combination of calibrators. An ANOVA statistical test and descriptive statistics were used to compare each set of results. Results: The UFH APTT had a mean range of 100.1–127.2 seconds. The 3.8% short draw tube had the highest mean. The ANOVA however was p=0.9845. The UFH FXa mean range with all 6 tubes was 0.32–0.37 IU/mL. The ANOVA for the UFH curve had a p value of 0.9878. With the HYBRID curve the mean range was 0.34–0.39 IU/mL with a p value of 0.9961. When comparing the six UFH results with the six HYBRID curves data the ANOVA p value was 0.9994. The CTAD tubes gave the highest levels of UFH. The LMWH APTT had a mean range of 37.1–41.2 seconds. The highest mean was the CTAD normal draw tube. The LMWH assay curves had a mean range of 0.37–0.46 IU/mL with the CTAD normal draw tube again having the high recovery of heparin. The ANOVA result had a p value of 0.9060. The HYBRID curve had a mean range of 0.42–0.49 IU/mL and again the CTAD normal draw tube displayed the highest amount of heparin. The ANOVA p value was 0.9379. When comparing the 6 LMWH results with the 6 HYBRID results the ANOVA p value was 0.9512. Discussion: The APTT results were skewed. In one subject the APTT was 48 seconds and another around 114 seconds with the same amount of UFH detected. This makes the so-called therapeutic range suspect. The UFH and LMWH data compared to the HYBRID curves was excellent clinically and statistically. This data demonstrates that the laboratory could use a single calibration curve for monitoring both UFH and LMWH subjects. The intentional short draw tube did not seem to affect the FXa assay. The FXa assay appears to be a better method monitoring heparin subjects than the APTT. The APTT was largely unaffected in subjects on LMWH and is not normally used to monitor individuals on this anticoagulant.


1993 ◽  
Vol 70 (06) ◽  
pp. 0909-0914 ◽  
Author(s):  

SummaryFibrin D-Dimer (D-Di), prothrombin activation fragment (F 1+2) and thrombin-antithrombin III complexes (TAT) were measured using ELISA procedures in the plasma of patients with an acute deep venous thrombosis (DVT), at presentation and on days 2, 6 and 10 after initiation of heparin treatment. Patients were randomly allocated into two treatment groups: 44 patients received adapted doses of continuous intravenous unfractionated heparin (UH) whereas 47 received 1 mg/kg every twelve hours of a low molecular weight heparin (enoxaparin) subcutaneously. A phlebography and a perfusion lung scan were performed before inclusion and on day 10. Failure of therapy (n = 9) was defined by venogram worsening or confirmed pulmonary embolism. Improvement (n = 44) or stationary state (n = 38) were defined by venogram evolution in the absence of new leg scan defects.At presentation, D-Di, F 1 + 2 and TAT were above cut-off values in 97, 66 and 89% of patients respectively. D-Di levels correlated with the extent of venous thrombosis whereas TAT and F 1 + 2 did not. Mean levels of D-Di decreased sharply during the first days of treatment but were still abnormal on day 10. A secondary increase of D-Di on days 6 or 10 by more than 3 μg/ml occurred in 4 of the 9 patients who developed a thromboembolic recurrence but in none of the 72 patients who had a more favorable outcome. F 1 + 2 and TAT time-courses were not related to clinical evolution. In the Enoxaparin group, there was no relationship between antifactor Xa activities and any biological markers. TAT and F 1 + 2 levels fell on day 2 and remained stable until day 10. In contrast, in the UH group, TAT and F 1 + 2 did not significantly decrease on day 2, probably due to a delay in dose adaptation, but they declined slowly until day 10.In conclusion, D-Di displays a higher sensitivity than F 1 + 2 or TAT for the diagnosis of D\T. D-Di, but not TAT or F 1 + 2, follow-up seems to be of potential value for early detection of recurrency. Hemostatic activation is controlled earlier by fixed doses of a low molecular weight heparin, irrespective of the plasma anti-factor Xa activities, than by unfractionated heparin at adapted doses.


1994 ◽  
Vol 72 (06) ◽  
pp. 942-946 ◽  
Author(s):  
Raffaele Landolfi ◽  
Erica De Candia ◽  
Bianca Rocca ◽  
Giovanni Ciabattoni ◽  
Armando Antinori ◽  
...  

SummarySeveral “in vitro” and “in vivo” studies indicate that heparin administration may affect platelet function. In this study we investigated the effects of prophylactic heparin on thromboxane (Tx)A2 biosynthesis “in vivo”, as assessed by the urinary excretion of major enzymatic metabolites 11-dehydro-TxB2 and 2,3-dinor-TxB2. Twenty-four patients who were candidates for cholecystectomy because of uncomplicated lithiasis were randomly assigned to receive placebo, unfractionated heparin, low molecular weight heparin or unfractionaed heparin plus 100 mg aspirin. Measurements of daily excretion of Tx metabolites were performed before and during the treatment. In the groups assigned to placebo and to low molecular weight heparin there was no statistically significant modification of Tx metabolite excretion while patients receiving unfractionated heparin had a significant increase of both metabolites (11-dehydro-TxB2: 3844 ± 1388 vs 2092 ±777, p <0.05; 2,3-dinor-TxB2: 2737 ± 808 vs 1535 ± 771 pg/mg creatinine, p <0.05). In patients randomized to receive low-dose aspirin plus unfractionated heparin the excretion of the two metabolites was largely suppressed thus suggesting that platelets are the primary source of enhanced thromboxane biosynthesis associated with heparin administration. These data indicate that unfractionated heparin causes platelet activation “in vivo” and suggest that the use of low molecular weight heparin may avoid this complication.


1993 ◽  
Vol 70 (04) ◽  
pp. 625-630 ◽  
Author(s):  
Edward Young ◽  
Benilde Cosmi ◽  
Jeffrey Weitz ◽  
Jack Hirsh

SummaryThe non-specific binding of anticoagulantly-active heparin to plasma proteins may influence its anticoagulant effect. We used low affinity heparin (LAH) essentially devoid of anti-factor Xa activity to investigate the extent and possible mechanism of this non-specific binding. The addition of excess LAH to platelet-poor plasma containing a fixed amount of unfractionated heparin doubled the anti-factor Xa activity presumably because it displaces anticoagulantly-active heparin from plasma proteins. Although dextran sulfates of varying molecular weights also increased the anti-factor Xa activity, less sulfated heparin-like polysaccharides had no effect. These findings suggest that the ability to displace active heparin from plasma protein binding sites is related to charge and may be independent of molecular size. In contrast to its effect in plasma containing unfractionated heparin, there was little augmentation in anti-factor Xa activity when LAH was added to plasma containing low molecular weight heparin (LMWH), indicating that LMWH binds less to plasma proteins than unfractionated heparin. This concept is supported by studies comparing the anticoagulant activity of unfractionated heparin and LMWH in plasma with that in buffer containing antithrombin III. The anti-factor Xa activity of unfractionated heparin was 2-fold less in plasma than in the purified system. In contrast, LMWH had identical anti-factor Xa activity in both plasma and buffer, respectively. These findings may be clinically relevant because the recovered anti-factor Xa activity of unfractionated heparin was 33% lower in plasma from patients with suspected venous thrombosis than in plasma from healthy volunteers. The reduced heparin recovery in patient plasma reflects increased heparin binding to plasma proteins because the addition of LAH augmented the anti-factor Xa activity. In contrast to unfractionated heparin, there was complete recovery of LMWH added to patient plasma and little increase of anti-factor Xa activity after the addition of LAH. These findings may explain why LMWH gives a more predictable dose response than unfractionated heparin.


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