Subcutaneous Unfractionated Heparin Research Articles

Unfractionated heparin for second trimester placental insufficiency: a pilot randomized trial

To conduct a pilot randomized controlled trial of unfractionated heparin (UFH) in women considered at high risk of placental insufficiency in the second trimester. Women with either false-positive first trimester (pregnancy-associated placental protein-A [PAPP-A] < 0.35 MoM) or second trimester (alpha-fetoprotein [AFP] > 2.0 MoM, inhibin > 3.0 MoM, human chorionic gonadotropin > 4.0 MoM) serum screening tests or medical/obstetric risk factors were screened for placental insufficiency by sonographic evaluation of the placenta and uterine artery Doppler between 18 and 22 weeks. Thrombophilia screen-negative women with two or three abnormal test categories were randomized by 23+6 weeks to self-administration of subcutaneous unfractionated heparin (UFH) 7500 IU twice daily until birth or 34 weeks, or to standard care. Maternal anxiety and other maternal-infant outcomes were determined. Thirty-two out of 41 eligible women consented, with 16 women randomized to UFH and 16 to standard care. There was no statistically significant difference identified between the two treatment groups (standard care vs. UFH) for the following: maternal anxiety score (mean [standard deviation]), 14.2 [± 1.6] vs. 14.0 [± 1.8]; birth weight (median [range]), 1795 [470-3295]g vs. 1860 [730-3050]g; perinatal death, 3 vs. 0; severe preeclampsia, 2 vs. 6; placental weight < 10th percentile, 7 vs. 4; or placental infarction, 4 vs. 3. Our study design identified women at high risk of adverse maternal-infant outcomes attributable to placental insufficiency. Women with evidence of placental insufficiency were willing to undergo randomization and self-administration of UFH without increased maternal anxiety.

Dosing Frequency of Unfractionated Heparin Thromboprophylaxis: A Meta-analysis

In medical patients, it is unclear whether thromboprophylaxis with low-dose unfractionated heparin (UFH) should be administered bid or tid. This study was a mixed-treatment comparison meta-analysis of randomized control trials that enrolled hospitalized nonsurgical patients at risk for VTE and compared UFH bid, UFH tid, or low-molecular-weight heparin (LMWH) to one another or to an inactive control subject. DVT, pulmonary embolism (PE), major bleeding, and death were measured. A Bayesian framework using a random-effects model was applied. Sixteen trials with moderate methodologic quality enrolling 27,667 patients contributed to this analysis. The relative risk and 95% credible intervals comparing UFH tid to UFH bid for DVT, PE, death, and major bleeding were 1.56 (0.64-4.33), 1.67 (0.49-208.09), 1.17 (0.72-1.95), and 0.89 (0.08-7.05), respectively. When compared with either dose of UFH, the use of LMWH has an effect similar to UFH on all four outcomes. Moderate-quality evidence suggests that subcutaneous UFH bid and UFH tid do not differ in effect on DVT, PE, major bleeding, and mortality. Either of the two dosing regimens of UFH or LMWH appears to be a reasonable strategy for thromboprophylaxis in medical patients. A future randomized trial comparing the two doses of UFH is very unlikely, considering the very large sample size that would be required to demonstrate a significant difference, which, if it exists, is undoubtedly small.

Anticoagulation therapy for hospitalized patients: Patterns of use, compliance with national guidelines, and performance on quality measures

The use of anticoagulant therapy for the prevention and treatment of venous thromboembolism (VTE) and acute coronary syndrome (ACS) among hospital inpatients was evaluated. Medication-use data were retrospectively collected on 1716 patients who received anticoagulants for VTE or ACS at 42 community hospitals during the period April-June 2009; all hospitals in the sample were members of the same large health care organization. Descriptive analyses were performed to characterize anticoagulant use, patient safety, compliance with national prescribing guidelines, and performance on relevant Joint Commission quality measures. The most common indications for anticoagulant use were VTE prophylaxis (67.5% of cases), ACS (13.5% of cases), and VTE treatment (11.9% of cases). The agents most commonly used for VTE prophylaxis were subcutaneous enoxaparin (70% of cases) and subcutaneous unfractionated heparin (UFH). Overall, the anticoagulant regimen used was consistent with national prescribing guidelines in 67.5% of cases; however, rates of appropriate prescribing were lower in subgroups of patients with renal impairment, obesity, or both (63.6%, 42.5%, and 63.6%, respectively). Reported anticoagulant-related adverse events during the study period mainly involved minor or major bleeding, which occurred in 36% and 32% of cases, respectively. Compliance with Joint Commission core measures ranged from 49.1% for core measure VTE-3 (warfarin overlap therapy) to 72.3% for VTE-4 (monitoring of UFH dosages and platelet counts by protocol). Among hospitals in a large national health care system, the most common use of anticoagulants in hospitalized patients was for VTE prevention, followed by ACS and VTE treatment. Enoxaparin and UFH were the most commonly used agents for each indication, and the selection and use of anticoagulants were in compliance with national guidelines in the majority of patients for whom those drugs were prescribed.

Use and outcomes of venous thromboembolism prophylaxis after spinal fusion surgery

The number of spinal fusion operations in the USA is rapidly rising, but little is known about optimal venous thromboembolism prophylaxis after spinal surgery. To examine the use of and outcomes associated with venous thromboembolism prophylaxis after spinal fusion surgery in a cohort of 244 US hospitals. We identified all patients with a principal procedure code for spinal fusion surgery in hospitals participating in the Premier Perspective database from 2003 to 2005, and searched for receipt of pharmacologic prophylaxis (subcutaneous unfractionated heparin, low molecular weight heparin, or fondaparinux) and/or mechanical prophylaxis (compression devices and elastic stockings) within the first 7 days after surgery. We also searched for discharge diagnosis codes for venous thromboembolism and postoperative hemorrhage during the index hospitalization and within 30 days after surgery. Among 80,183 spinal fusions performed during the time period, cervical fusions were the most common (49.0%), followed by lumbar fusions (47.8%). Thromboembolism prophylaxis was administered to 60.6% of patients within the first week postoperatively, with the most frequent form being mechanical prophylaxis alone (47.6%). Of the 244 hospitals, 26.2% provided prophylaxis to ≥ 90% of their patients undergoing spinal fusion; however, 33.2% provided prophylaxis to fewer than 50% of their patients. The rate of diagnosed venous thromboembolism within 30 days after surgery was 0.45%, and the rate of postoperative hemorrhage was 1.1%. Substantial variation exists in the use of thromboembolism prophylaxis after spinal fusion surgery in the USA. Nevertheless, overall rates of diagnosed thromboembolism after spinal fusion appear to be low.

Use of thromboelastography to guide thromboprophylaxis after caesarean section

Background Thromboprophylaxis is commonly required following caesarean section. However the effect of thromboprophylactic dosages of subcutaneous heparin on coagulation is unknown because conventional laboratory tests are largely unaffected. The aim of this study was to determine if thromboelastography could detect and quantify the effect of unfractionated heparin on coagulation profile when given at the time of surgery. Methods Nineteen women undergoing elective caesarean section were recruited. Blood samples collected before and after administration of subcutaneous unfractionated heparin 7500 IU underwent thromboelastography using both plain and heparinase cuvettes. Anti-factor Xa levels were also measured. Results There was a significant difference in R times between plain and heparinase samples (−10.6%, P = 0.0072) indicating that thromboelastography could detect an effect of unfractionated heparin. Compared to baseline there were significant decreases of R times in plain (−20.4%, P = 0.033) and heparinase (−28.8%, P = 0.0001) samples despite the administration of unfractionated heparin. Anti-factor Xa levels were virtually undetectable (mean 0.01 U/mL). Conclusion Thromboelastography was able to detect and quantify the effect of unfractionated heparin on blood coagulability, an effect not detected by conventional laboratory tests. Thromboelastography demonstrated a pro-coagulant effect of surgery that was only partially mitigated by the use of unfractionated heparin. In this study, at a dose of 7500 IU subcutaneous unfractionated heparin appears to have little anticoagulant effect.

Repeated Doses of Oral and Subcutaneous Heparins Have Similar Antithrombotic Effects in a Rat Carotid Arterial Model of Thrombosis

Although heparins are usually injected intravenously or subcutaneously, antithrombotic activity is observed in rat models following single oral heparin doses. Since repetitive dosing is usually needed for thromboprophylaxis, study objectives were to determine whether repetitive oral heparin prevented arterial thrombosis and to compare effectiveness to subcutaneous administration. Wistar rats were given subcutaneous or oral unfractionated heparin ([UFH] 1 mg/kg per 48 h), low-molecular-weight heparin ([LMWH] tinzaparin, 0.1 mg/kg per 12 h), or saline for 30 days. On the last day, thrombosis was initiated by placing 30% FeCl(3)-soaked filter paper on the distal carotid. Subsequent flow measurements, for a 60-minute period, included recorded time of initial thrombus formation (time till thrombus begins [TTB]), and time until carotid occlusion (time till occlusion [TTO]). The formed thrombus was dried and weighed. The activated partial thromboplastin time (aPTT), anti-factor Xa, and antithrombin activity were determined from the plasma. Both oral and subcutaneous heparins significantly increased TTB and TTO. Time of initial thrombus formations were 12.6 ± 1.1, 21.2 ± 2.2, 25.3 ± 3.9, 21.7 ± 3.1, and 21.3 ± 1.7 minutes and TTOs were 29.3 ± 3.6, 54.8 ± 4.0, 60.0 ± 0.3, 56.7 ± 3.3, and 58.3 ± 1.7 minutes (mean ± SEM) for control, subcutaneous UFH, oral UFH, subcutaneous LMWH, and oral LMWH, respectively. Thrombus weight was 2.52 ± 0.29 g in control and was reduced to 43%, 23%, 33%, and 28% of control weight for subcutaneous UFH, oral UFH, subcutaneous LMWH, and oral LMWH, respectively. Thrombus weight was significantly less for oral compared to subcutaneous UFH. The aPTT for oral UFH, and anti-factor Xa activity in the LMWH-treated groups were significantly greater than control (two-tailed t tests). These findings confirm that orally administered heparins are absorbed. Repeated treatment with oral heparin showed similar antithrombotic activity compared to subcutaneous heparin. Oral heparin use for arterial thromboprophylaxis should be further investigated.

Safety profile of tinzaparin versus subcutaneous unfractionated heparin in elderly patients with impaired renal function treated for acute deep vein thrombosis: The Innohep® in Renal Insufficiency Study (IRIS)

IntroductionTrials comparing the use of full dose unfractionated heparin (UFH) or low molecular weight heparins (LMWHs) in very elderly patients with impaired renal function are lacking. IRIS aimed to assess whether LMWH is at least as safe as UFH in this population. Materials and methodsThe study included renally impaired patients ≥70years with acute symptomatic lower limb deep vein thrombosis (DVT). Patients were randomized to initial treatment with either tinzaparin 175IU/kg once daily (n=269) or activated partial thromboplastin time-adjusted UFH twice daily (n=270). After acute management both groups received vitamin K antagonist to day 90. ResultsThe trial was stopped prematurely due to a difference in mortality favoring the UFH group (11.5 vs. 6.3%; p=0.035). Rates of clinically relevant bleedings by day 90 were similar in the tinzaparin (11.9%) and UFH (11.9%) groups, as were rates of confirmed recurrent venous thromboembolism (VTE) (2.6 vs. 1.1%; p=0.34). As the mortality difference could not be explained by bleedings or recurrent VTE, a post-hoc analysis was performed. This identified six baseline characteristics significantly correlated with mortality, of which five were over-represented in the tinzaparin group. ConclusionThe IRIS study was a challenging study involving patients (mean age 83years) usually excluded from clinical studies, but its early termination has left questions unanswered. The mortality difference observed with tinzaparin vs. UFH in elderly, renally-impaired patients with DVT cannot be explained on the basis of bleedings or recurrent VTE, and may reflect an imbalance of mortality risk factors at baseline.

Safety and Efficacy of Prophylactic Anticoagulation in Patients with Traumatic Brain Injury

Patients with traumatic brain injury (TBI) are at high risk for venous thromboembolism (VTE), but physicians are cautious with chemical prophylaxis in these patients because of concern about exacerbating intracranial hemorrhage. We hypothesized that early use of chemical thromboprophylaxis would reduce VTE incidence without increasing intracranial hemorrhage. Records of all patients admitted with a TBI to a Level I trauma center from 2006 to 2008 were reviewed. TBI was defined as intracranial hemorrhage, hematoma, contusion, or diffuse axonal injury with a head Abbreviated Injury Scale score >2. Patients were excluded if they were discharged or died within 72 hours of admission. Chemical prophylaxis was defined as subcutaneous or intravenous unfractionated heparin or low molecular weight heparin before any VTE diagnosis. Progression of TBI was defined by worsening CT findings. VTE was defined as deep venous thrombosis or pulmonary embolus confirmed by radiology reports. Primary outcomes were progression of hemorrhage and VTE events. Eight hundred and twelve of the 1,258 patients admitted to the trauma center with a TBI met study criteria. Chemical thromboprophylaxis was given to 49.5% (n = 402). Mean head Abbreviated Injury Scale score was 3.4 in both groups. One hundred and sixty-nine patients started prophylaxis within 48 hours and 242 patients began within 72 hours. Patients receiving chemical prophylaxis had a lower incidence of VTE (1% versus 3%; p = 0.019). Although not statistically significant, they also had a lower rate of injury progression, 3% versus 6% (p = 0.055). Use of chemical thromboprophylaxis in TBI patients with a stable or improved head CT after 24 hours substantially reduces the incidence of VTE and does not increase the risk of progression of intracranial hemorrhage.

Individual patient data meta‐analysis of enoxaparin vs. unfractionated heparin for venous thromboembolism prevention in medical patients

Unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) are both recommended for venous thromboembolism (VTE) prophylaxis in hospitalized medical patients. To perform an individual patient data meta-analysis to evaluate the relative efficacy and safety of the LMWH enoxaparin and UFH in preventing VTE in hospitalized medical patients. Randomized clinical trials comparing subcutaneous enoxaparin (4000 IU once-daily) and UFH (5000 IU subcutaneous two- or three-times daily) for VTE prevention were identified by a systematic search. Individual patient data were obtained from each eligible trial. Overall, four trials were eligible, including 3600 patients randomized to receive enoxaparin (n = 1799) or UFH (n = 1801). Median patient age was 71 years, and 49.3% were female. Compared with UFH, enoxaparin was associated with risk reductions of 37% for total VTE [relative risk (RR) 0.63, 95% confidence interval (CI) 0.51-0.77] and 62% for symptomatic VTE (RR 0.38, 95% CI 0.17-0.85) at day 15. RR for total VTE in stroke and non-stroke patients was 0.59 (95% CI 0.47-0.74) and 0.87 (95% CI 0.51-1.50), respectively. Major bleeding rates were consistently low and similar between treatment groups at day 15 (RR 1.13, 95% CI 0.53-2.44). There was a trend towards reduced risk for mortality in patients receiving enoxaparin (RR 0.83, 95% CI 0.64-1.08), compared with UFH. Enoxaparin significantly reduces VTE in hospitalized medical patients, compared with UFH, without increasing the risk for major bleeding, and was associated with a trend towards reduced all-cause mortality.

P.19 Sensitivity to subcutaneous and intravenous unfractionated heparin (UFH) at delivery

P.19 Sensitivity to subcutaneous and intravenous unfractionated heparin (UFH) at delivery

Pharmacological Deep Vein Thrombosis Prophylaxis Does Not Lead to Hematoma Expansion in Intracerebral Hemorrhage With Intraventricular Extension

Patients with intracerebral hemorrhage (ICH) are at high risk for development of deep venous thrombosis. Current guidelines state that low-dose subcutaneous low molecular weight heparin or unfractionated heparin may be considered at 3 to 4 days from onset. However, insufficient data exist on hematoma volume in patients with ICH before and after pharmacological deep venous thrombosis prophylaxis, leaving physicians with uncertainty regarding the safety of this practice. We identified patients from our stroke registry (June 2003 to December 2007) who presented with ICH only or ICH+intraventricular hemorrhage and received either low molecular weight heparin subcutaneously or unfractionated heparin within 7 days of admission and had a repeat CT scan performed within 4 days of starting deep venous thrombosis prophylaxis. We calculated the change in hematoma volume from the admission and posttreatment CTs. Hematoma volume was calculated using the ABC/2 method and intraventricular hemorrhage volumes were calculated using a published method of hand drawn regions of interest. We identified 73 patients with a mean age of 63 years and median National Institutes of Health Stroke Scale score 11.5. The mean baseline total hematoma volume was 25.8 mL±23.2 mL. There was an absolute change in hematoma volume from pre- and posttreatment CT of -4.3 mL±11.0 mL. Two patients developed hematoma growth. Repeat analysis of patients given pharmacological deep venous thrombosis prophylaxis within 2 or 4 days after ICH found no increase in hematoma size. Pharmacological deep venous thrombosis prophylaxis given subcutaneously in patients with ICH and/or intraventricular hemorrhage in the subacute period is generally not associated with hematoma growth.

Does Prophylactic Subcutaneous Heparin Increase the Risk of Wound Infection after Colorectal Surgery?

Chemical prophylaxis using unfractionated heparin (UH) and low-molecular weight heparin is used in surgical patients to prevent venous thromboembolism. There is some evidence that prophylactic doses of heparin may increase the rate of surgical site infection (SSI) after elective orthopedic procedures. Little is known regarding the effect of heparin on SSI after colorectal procedures. We performed this study to study the effect of prophylactic unfractionated heparin on the rate of SSI after colorectal procedures. We did a retrospective analysis of 155 consecutive cases of patients of a single colorectal surgeon who underwent colorectal resection. Subcutaneous unfractionated heparin was given to 52 patients (29%). The rate of SSI in the group that received UH was 33 per cent versus 28 per cent in the group that did not receive UH (P = 0.31). There was also no significant effect of prophylactic heparin on SSI noted among any patient subgroup. The use of prophylactic unfractionated heparin after colorectal procedures does not seem to increase the rate of surgical site infection.

Subcutaneous Unfractionated Heparin for Treatment of Venous Thromboembolism in End-Stage Renal Disease

To report 3 cases of venous thromboembolism (VTE) in patients with end-stage renal disease (ESRD) treated with subcutaneous unfractionated heparin (UFH) bridged with warfarin. Three patients with ESRD were successfully treated for VTE with unmonitored, fixed-dose subcutaneous UFH every 12 hours and dose-adjusted warfarin. The first patient was initiated on continuous infusion UFH for deep-vein thrombosis, but due to poor vascular access, nurses were unable to consistently measure anti-Xa levels. Therefore, subcutaneous UFH 17,500 units (∼245 units/kg/dose) every 12 hours was initiated. Oral warfarin 5 mg/day was started the following day. The patient received 4 days of inpatient subcutaneous UFH and then was discharged to complete the bridge as an outpatient. The second patient received subcutaneous UFH 10,000 units (∼244 units/kg/dose) every 12 hours and oral warfarin 2.5 mg/day to treat a nonocclusive thrombus along her right femoral vein hemodialysis catheter. The patient received 1 day of inpatient subcutaneous UFH treatment prior to discharge and continued bridge therapy with warfarin as an outpatient. The third patient was initiated on subcutaneous UFH 20,000 units (∼223 units/kg/dose) every 12 hours and oral warfarin 7.5 mg/day due to a subtherapeutic INR (1.50) 5 days after receiving fresh frozen plasma to reduce her therapeutic INR for a procedure. The patient received 2 doses of subcutaneous UFH as an inpatient before treatment was discontinued because her INR was therapeutic at 2.3. Subcutaneous UFH has been used to treat VTE since the early 1980s; however, with the advent of low-molecular-weight heparin (LMWH), subcutaneous UFH use diminished. Several studies comparing the use of subcutaneous UFH to both continuous infusion UFH and LMWH concluded that subcutaneous UFH is a safe and efficacious alternative. The 2008 Chest Guidelines for Antithrombotic Therapy for Venous Thromboembolic Disease support the use of subcutaneous UFH for the treatment of VTE with a Grade 1A recommendation and provide a Grade 2C recommendation for use of UFH over LMWH for patients with VTE and severe renal failure. Safe and convenient treatment options for VTE in patients with ESRD are limited. Fixed-dose, unmonitored subcutaneous UFH as a bridge to warfarin therapy is an effective option in patients with ESRD and those with financial restrictions. The pharmacist plays a key role in identifying patients for whom subcutaneous UFH treatment may be a viable alternative, recommending an appropriate dosing regimen, and educating health-care professionals and patients about safe use.

Parnaparin: A Review of its Safety and Efficacy

Introduction: Parnaparin, a low molecular weight heparin (LMWH), has a greater anti-thrombotic to anticoagulant activity ratio in comparison with unfractionated heparin (UFH). Moreover, its subcutaneous administration permits a greater bioavailability and a longer half-life than UFH, allowing a more practical once-daily dosage. Objective: To evaluate the methodology and cumulative evidence presented in systematic reviews and in clinical trials about the safety and efficacy of parnaparin use in vascular disorders. Materials and methods: Electronic literature sources were used to identify parnaparin trials and reviews published from 1984 to April 2010. The search was carried out in MEDLINE, EMBASE and PASCAL; search terms were “parnaparin” or “parnaparin sodium” or “fluxum”. We identified various trials regarding parnaparin and its use in the prevention and treatment of venous disorders, in the treatment of acute coronary syndromes and peripheral arterial occlusive disease (PAOD), and we found a recent parnaparin trial in the treatment of retinal vein occlusion. We included two reviews regarding the clinical use of the drug. Conclusion: Parnaparin has been shown to be safe and effective for the prevention and treatment of venous thromboembolism, for the treatment of acute coronary syndromes and PAOD. Subcutaneous parnaparin is at least as effective as subcutaneous UFH in preventing deep venous thrombosis and pulmonary embolism. In the treatment of patients with acute coronary syndrome, subcutaneous parnaparin is associated with a lower incidence of a triple composite endpoint of death, acute MI or need for myocardial revascularization. Long-term treatment with subcutaneous parnaparin in patients with PAOD significantly improves time and distance of pain-free walking compared with baseline. In the treatment of patients with retinal vein occlusion parnaparin seems to be more effective than aspirin in preventing functional worsening. Parnaparin is a useful option in the range of LMWHs for the prevention and treatment of the several vascular disorders.

Validation of a dosing regimen for fixed-dose, weight-adjusted, subcutaneous unfractionated heparin for the acute treatment of venous thrombo-embolism in a population from a resource-constrained environment

A study in Canada and New Zealand (Kearon et al.) suggested that fixed-dose unmonitored subcutaneous (SC) unfractionated heparin (UFH) is as effective and safe as low-molecular-weight heparin (LMWH) for the acute treatment of venous thrombo-embolism. While this trial has limitations, it provides evidence to support the use of SC UFH in a resource-constrained environment. However, because public sector patients with VTE in South Africa often have multiple co-morbidities and are thinner and younger than those in that study, the local validity of the published dosing regimen is unclear.

Tinzaparin Sodium

Tinzaparin sodium (Innohep) is a low molecular weight heparin (LMWH) that is effective in the prevention and treatment of deep vein thrombosis (DVT) and/or pulmonary embolism (PE), and in maintaining the patency of haemodialysis circuits in adult patients. In terms of preventing DVT and/or PE, therapy with subcutaneous tinzaparin sodium was more effective than oral warfarin and equivalent to subcutaneous enoxaparin sodium in patients undergoing orthopaedic surgery, and did not significantly differ from that of subcutaneous unfractionated heparin (UFH) in patients undergoing general surgery. In the initial therapy of adult patients with DVT and/or PE, subcutaneous tinzaparin sodium was at least as effective as intravenous UFH and did not significantly differ from subcutaneous dalteparin sodium. Various other studies have demonstrated that the long-term efficacy of subcutaneous tinzaparin sodium in the treatment of patients with DVT and/or PE was sustained for a total period of up to 12 months. Tinzaparin sodium was also demonstrated to be effective in maintaining the patency of haemodialysis circuits in adult patients with end-stage renal failure. In clinical studies, tinzaparin sodium was generally well tolerated in the prevention and treatment of DVT and/or PE in adult patients, including in elderly patients, and in patients undergoing haemodialysis. As expected, bleeding complications were the most frequently occurring adverse event. Thus, available data indicate that tinzaparin sodium is a useful option in the prevention and treatment of DVT and/or PE, and in maintaining the patency of haemodialysis circuits in adult patients.

Use of therapeutic dose low molecular weight heparin during pregnancy in women with mechanical heart valves

Management of anticoagulation in women with mechanical heart valves (MHV) is one of the most challenging issues faced by obstetric physicians who manage pregnant women with cardiac problems. The already high risk of valve thrombosis is increased further during pregnancy because of the prothrombotic changes of pregnancy. The safest option for the mother, to reduce the risk of valve thrombosis leading to valve failure or systemic thromboembolism, is to remain on oral anticoagulants such as warfarin. However, warfarin crosses the placenta with a 5–6% risk of warfarin embryopathy if taken between six and nine weeks gestation.1 In addition, warfarin anticoagulates the fetus and there is a high rate of late fetal loss, up to 40% in some studies,2 which further increases women's reluctance to continue taking this form of anticoagulation. Heparin, which does not cross the placenta, is an effective alternative to warfarin for treatment and prevention of venous thrombosis during pregnancy, but there are concerns relating to its efficacy as an anticoagulant in women with MHV. Subcutaneous unfractionated heparin, even when given in high and monitored doses, is associated with an unacceptably high rate of maternal thrombosis. The more predicable anticoagulant effect of low molecular weight heparin (LMWH) makes it is an attractive agent for use in this clinical situation but there are limited data relating to its safety and efficacy. In 2004, Oran and co-workers3 reviewed published case reports and case series of LMWH use in pregnant women with MHV. The overall rate of thromboembolic complications in 81 pregnancies was 11.1% but four of these events were reported in single case studies. Monitoring of anti-Xa levels was not carried out in all centres and women received LMWH for variable periods during pregnancy. Such discrepancies make it difficult to extrapolate these data to other situations.

Prolonged activated partial thromboplastin time in thromboprophylaxis with unfractionated heparin in patients undergoing cesarean section

Hemorrhage is an important complication of heparin-thromboprophylaxis after surgery. We attempted to clarify the incidence rate of prolonged activated partial thromboplastin time (APTT), representative of hemorrhagic tendency, in Japanese women who received thromboprophylaxis with unfractionated subcutaneous heparin administration after cesarean section (CS). We also determined factors which affected postoperative APTT. We studied 280 women who were administered thromboprophylaxis with unfractionated subcutaneous heparin 5000 IU two times per day after CS. Postoperative APTT under heparin was measured and the incidence of its prolongation was determined. Preoperative APTT, blood loss during surgery, postoperative hematocrit, postoperative serum total protein level, and postpartum body weight were measured, and their correlation with postoperative APTT was determined. Preoperative and postoperative APTT values were 28.3 (26.7-30.3) and 33.8 (31.0-37.5) seconds for median (interquartile range), respectively. Overall, 7.1% of patients showed >or=45 s postoperative APTT. Two patients (0.7%) showed >or=60 s APTT, one of whom suffered subcutaneous hemorrhage around the abdominal incision with complete healing. There were no other hemorrhagic complications. Preoperative APTT positively, and postpartum body weight inversely, correlated with postoperative APTT. The amount of blood loss, postoperative hematocrit, and postoperative serum total protein level did not correlate with postoperative APTT. No discernible deep vein thrombosis or pulmonary embolism occurred. Although 7.1% of women under heparin-thromboprophylaxis showed a prolonged APTT that was 150% of the preoperative APTT, serious side effects were not observed. Subcutaneous administration of unfractionated heparin, if checking APTT prolongation 1 day after surgery, may be safe method of thromboprophylaxis after CS.

Comparison of pain and ecchymosis with low-molecular-weight heparin vs. unfractionated heparin in patients requiring bridging anticoagulation after warfarin interruption: a randomized trial

Subcutaneous (SC) low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH) are safe and efficacious for bridging anticoagulation after warfarin interruption. Although LMWH and UFH are self-administered by >90% of patients, factors that may be important to patients such as differences in pain and ecchymosis have not been explored. We randomized 24 patients to receive SC LMWH or SC UFH twice-daily during the perioperative period. Injection associated pain was recorded using a visual analogue scale and area of ecchymosis was measured by digital photography of the injection site on the day of the procedure. The area of ecchymosis was 2-fold higher with UFH than LMWH (19.4 cm(2) vs. 8.98 cm(2); P = 0.33) and pain was similar with both treatments (115 mm vs. 171 mm; P = 0.25), though neither finding attained statistical significance. This exploratory study was underpowered to detect differences between the groups. Further studies are needed to reliably compare pain and ecchymosis in LMWH vs. UFH.

Activated partial thromboplastin time monitoring in patients receiving unfractionated heparin for venous thromboembolism in relation to clinical outcomes

Venous thromboembolism (VTE) is a prevalent and serious condition, which requires anticoagulation treatment for prolonged time duration. The use of unfractionated heparin administered intravenously or subcutaneously for acute management of VTE has been studied with favourable clinical results. Most physicians use activated partial thromboplastin time to monitor the treatment effect, in an effort to obtain better efficacy with less bleeding complications. Recent data however does not support this practice. We set to explore the medical literature for the correlation between the level of anticoagulation and the clinical outcomes. Randomised controlled trials comparing subcutaneous unfractionated heparin to any other treatment modality in patients with venous thromboembolism were obtained and a meta-analysis was performed. Seventeen reports from 15 randomised controlled trials were included. Of these, eleven included anticoagulation measurements. Seven and six trials were included in our analysis for subcutaneous and intravenous modes of administration, respectively. No correlation between the anticoagulation level and the major clinical outcomes were found, except for the initial anticoagulation measurement and the total mortality at three months, but not to death related to treatment or disease progression. In conclusion, weight-adjusted subcutaneous unfractionated heparin without anticoagulation monitoring may be feasible for patients with acute venous thromboembolism. No differences exist between intravenous and subcutaneous modes of administration with regards to the correlation between anticoagulant measures and the clinical outcomes. More research is needed to substantiate this observation.