Low-dose Heparin Group Research Articles

Optimal antithrombotic regimen in patients with cardiogenic shock on ImpellaTM mechanical support: less might be more

Abstract Background Bleeding and ischemic complications are the main cause of morbidity and mortality in critically ill cardiogenic shock patients, supported by short-term percutaneous mechanical circulatory support (pMCS) devices. Hence, finding the optimal antithrombotic regimen is challenging. Bleeding not only occurs because of heparin and antiplatelet therapy (both required in the prevention of pump and acute stent thrombosis) but also because of device- and disease related coagulopathy. To prevent clotting-related device failure, most centers target full therapeutic heparin anticoagulation levels in left ventricular (LV) Impella™ supported patients in analogy with Veno-Arterial Extracorporeal Membrane Oxygenation. We aimed to investigate the safety (related to bleeding and thrombotic complications) of targeting low-dose versus therapeutic heparin levels in left Impella™-supported cardiogenic shock patients on dual antiplatelet therapy (DAPT). Methods In this hypothesis generating pilot study, we investigated 114 patients supported for at least two days by LV Impella™ mechanical support due to cardiogenic shock at three tertiary ICUs, highly specialized in mechanical support. Low-dose heparin (aPTT 40–60s or anti-Xa 0.2–0.3) was compared to standard of care (aPTT 60–80s or anti-Xa 0.3–0.5). Major adverse cardio- and cerebrovascular events (MACCE; composite of death, myocardial infarction, stroke/transient ischemic attack) and BARC bleeding (bleeding academic research consortium classification) during 30 day follow-up were assessed. Inverse probability of treatment weighting (IPTW) analysis was calculated with age, gender, arterial hypertension, diabetes mellitus, smoking, chronic kidney disease, previous stroke, previous myocardial infarction, previous coronary arterial bypass grafting, hypercholesterolemia and DAPT as matching variables. COX regression analysis was conducted to test for robustness. Results IPTW revealed 52 patients in the low-dose heparin group and 62 patients in the therapeutic group. Mean age of patients after IPTW was 62±16 years in the intermediate and 62±13 years in the therapeutic group (p=0.99). 25% and 42.2% were male (p=0.92). Overall bleeding events and major (BARC3b) bleeding events were higher in the therapeutic heparin group (overall bleeding: Hazard ratio [HR]=2.58, 95% confidence interval [CI] 1.2–5.5; p=0.015; BARC 3b: HR=4.4, 95% CI 1.4–13.6, p=0.009). Minor bleeding (BARC3a) as well as MACCE and its single components (ischemic events) did not differ between both groups. These findings were robust in the COX regression analysis. Conclusion In this pilot analysis, low-dose heparin in 114 LV Impella™ cardiogenic shock patients was associated with less bleeding without increased ischemic events, adjusted for DAPT. Reducing the target heparin levels in critically ill patients supported by LV Impella™ might improve the outcome of this precarious group. These findings need to be validated in randomized clinical trials. Funding Acknowledgement Type of funding source: None

Appropriate Use of Intravenous Unfractionated Heparin after Digital Replantation: A Randomized Controlled Trial Involving Three Groups.

The purpose of this study was to clarify the appropriate use of unfractionated heparin as an anticoagulation agent after digital replantation. This study was a prospective, randomized, single-blind, blinded-endpoint method, three-arm, parallel-group, controlled clinical trial conducted at a single institution. A total of 88 patients (101 fingers) following digital amputation and subsequent repair by anastomosis of both arteries and veins were randomly allocated into three groups: (1) control group (no heparin dose), (2) low-dose heparin group (10,000 IU/day), and (3) high-dose heparin group (start at 15,000 IU/day, then adjust the dose to achieve an activated partial thromboplastin time of 1.5 to 2.5 times the baseline). The outcomes were assessed regarding the proportion of success at 2 weeks after replantation of amputated digits, total or partial necrosis, and occurrence of complications. No significant differences were found among the three groups, except for complications of congestion. The odds ratio of the heparin group compared with the control group for a success proportion was 5.40 (95 percent CI, 0.85 to 34.20; p = 0.027) in subjects aged 50 years or older. Significant elevations of activated partial thromboplastin time, aspartate transaminase, and alanine aminotransferase occurred in high-dose heparin groups on day 7. Unfractionated heparin administration is considered effective for patients aged 50 years or older, although the routine use of unfractionated heparin is not necessary after digital replantation. Therapeutic, II.

Does Low-Dose Heparin Have a Significant Role in Free Flap Surgery?

BackgroundIt is controversial issue that heparin decreases thrombosis for microsurgical anastomosis, and its effective role is under discussion. This study is for proving whether low-dose heparin is preventing thrombosis in free flap reconstruction.MethodsThrough chart reviews of 134 patients, using low-dose heparin for free tissue transfer from 2011 to 2016, retrospective analysis was performed. 33 patients received low-dose heparin therapy after surgery. And 101 patients received no-heparin therapy. Complications included flap necrosis, hematoma formation, dehiscence and infection.ResultsIn no-heparin therapy group, comparing the flap necrosis revealed 16 cases (15.84%). And, flap necrosis was 6 cases (18.18%) in low-dose heparin therapy group. The statistical analysis of flap necrosis rate showed no significant difference (p=0.75). The results showed that there was no significant difference of flap necrosis rate between two groups.ConclusionIn this study, patients in the low-dose heparin group had no significantly lower rates of flap failure compared with no-heparin group. This suggests that low-dose heparin may not prevent thrombosis and subsequent flap failure to a significant extent.

Low-dose Heparin Therapy During Living Donor Right Hepatectomy Is Associated With Few Side Effects and Does Not Increase Vascular Thrombosis in Liver Transplantation

BackgroundAt many centers, various heparin doses have been administrated systemically during living donor partial hepatectomy in an effort to minimize the potential for graft vascular thrombosis, which could lead to delayed graft function. However, there is no consensus regarding the advisability of heparin administration during living donor hepatectomy for liver transplantation. MethodsWe prospectively enrolled 270 donors between 2005 and 2011 to investigate donor and recipient outcomes between a low dose (25 IU/kg) and a conventional dose of heparin (50 IU/kg). ResultsThe low-dose heparin group did not show an increased incidence of vascular thrombosis: the rates of hepatic artery and portal vein thromboses were not significantly different between the two groups (P = .935 and P = .158, respectively). In addition, injection of low-dose heparin reduced donor complications with significant differences in postoperative hospital stay (P < .001), donor operative time (P < .001), hemoglobin/hematocrit decrease (P = .05/P = .02) and hemorrhagic complications (P = .004). ConclusionsAdministration of low-dose heparin during living donor hepatectomy can be used without worsening vascular thrombosis or donor complications.

Impact of heparin on coagulation index during the therapy of molecular adsorbent recirculating system in patients with liver failure

To investigate the impact of coagulative parameters on different anticoagulation systems in molecular adsorbent recirculating system (MARS) in subjects with liver failure, and to evaluate the safety of different anticoagulation methods . A prospective experimental observation was designed. According to anticoagulation Methods , 174 MARS treatment sessions for 146 patients with liver failure and prothrombin time activity percentage (PTA) ≤ 40% were randomly divided into 2 groups: 92 MARS treatment sessions in the heparin-free group and 82 in the low-dose heparin group. Time points of 0, 0.5, 1, 2, 3, 4, 5 and 6 h were selected to observe the coagulation changes of prothrombin time (PT), PTA, thrombin time (TT), activated partial thromboplastin time (APTT) and international normalized ratio (INR) dynamically. Adverse events such as line / filter coagulation, rupture and bleeding were also investigated and compared due to frequency and severity between the 2 groups. There was no difference in PT, PTA, INR between the 2 groups, but significant differences were observed in APTT and TT and fibrinogen (Fbg). APTT and TT levels in the low-dose heparin group was increased rapidly after the first given dose of anticoagulant heparin and reached the peak within 30 min.The levels at each time point was statistically different between the 2 groups (P<0.05). A significant difference in the Fbg level was obtained between the 2 groups. In the low-dose heparin group it was stabilized and increased slightly at the end of the treatment. While in the heparin-free group it was decreased gradually and reached a ravine at the end of the treatment. A curve was observed after 2.5 h treatment between the 2 groups (P=0.001). There were 2 cases of severe bleeding after MARS was finished in the heparin group, and 1 was terminated because of degree III clotting in the heparin-free group. Fibrinogen should be adsorbed while the blood touches the MARS circuit path and anticoagulants can prevent it. Comprehensive analysis of blood platelet count (BPC), fibrin degradation products (FDP), D-dimer and clinical symptoms is critical and required to determine the coagulation status to select an anticoagulation system before MARS. The use of low dose heparin in MARS improves the disorder of hypercoagulable state during the high coaguation period, while heparin-free during low coagulation period can effectively prevent the occurrence of bleeding and improve the mechanism of blood coagulation by reducing heparin-like substance in the blood.

Coagulation-Fibrinolysis Changes During Off-Pump Bypass: Effect of Two Heparin Doses

To date, no study has tested the effect of different heparin dosages on the hemostatic changes during off-pump coronary artery bypass graft (OPCABG) surgery, and a wide variety of empirical anticoagulation protocols are being applied. We tested the effect of two different heparin dosages on the activation of the hemostatic system in patients undergoing OPCABG procedures. Forty-two patients eligible for OPCABG procedures were assigned in a randomized fashion to low-dose heparin (150 IU/kg) or high-dose heparin (300 IU/kg). Prothrombin fragment 1+2, plasmin/alpha(2)-plasmin inhibitor complex, D-dimer, soluble tissue factor, tissue factor pathway inhibitor, total thrombin activatable fibrinolysis inhibitor (TAFI), and activated TAFIa were assayed by specific enzyme-linked immunosorbent assays at six different timepoints, before, during, and after surgery. Platelet function was evaluated by means of an in vitro bleeding time test, platelet function analyzer-100. The OPCABG surgery was accompanied by significant changes of all plasma biomarkers, indicative of systemic activation of coagulation and fibrinolysis. A significant increase in circulating TAFIa was detected perioperatively and postoperatively, and multiple regression analysis indicated that prothrombin F1+2 but not plasmin/alpha(2)-antiplasmin complex was independently associated with TAFIa level. Platelet function analyzer-100 values did not change significantly after OPCABG. All hemostatic changes were similar in the two heparin groups, even perioperatively, when the difference in anticoagulation was maximal. Both early and late hemostatic changes, including TAFI activation, are similarly affected in the low-dose and high-dose heparin groups, suggesting that the increase in heparin dosage is not accompanied by a better control of clotting activation during OPCABG surgery.

Appropriate dosage of unfraction heparin and low molecular weight heparin in hemodialysis patients

To investigate the appropriate dose of unfraction heparin and low molecular weight heparin (LMWH) in hemodialysis patients. Thirty-eight hemodialysis patients were enrolled and randomly allocated into four groups.The initial bolus dose for the Low-dose (LH, n = 10) and high-dose heparin (HH, n = 10) groups were 35 U/kg and 55 U/kg, respectively.The repeated maintenance dose for both groups were 10 U/kg.h and 16 U/kg.h, respectively. Fragmin were administered as single bolus (60 U/kg or 80 U/kg) at 30 minutes before hemodialysis in Low-dose LMWH(LLMWH, n = 10) and High-dose LMWH (HLMW, n = 8) group, respectively. Furthermore, the dialysis circuits in LUFH and LLMWUFH groups were primed with with 4 mg/dl heparinized saline before hemodialysis. Glass bead active clotting time (gbACT), clot rate (CR) and platelet function (PF) were examined using Sonoclot analysator at 0 h, 2 h and the end of hemodialysis at the arterial circuit and 2 h at the venous circuit. (1) LH and LUFH: the increase of gbACT and decrease of CR at the arterial circuit and the venous circuit at 2 h of hemodialysis were significant compared with baseline. While they recovered at the end of hemodialysis. No difference between the two groups at different time points was found, either. (2) LLMWH: No change were found in gbACT during hemodialysis. CR at the arterial circuit and the venous circuit were significantly decreased at 2 h and recovered at the end of hemodialysis. (3) LLMWUFH: gbACT at the arterial circuit was significantly increased only at 2 h of hemodialysis. CR at the arterial circuit and the venous circuit at 2 h of hemodialysis were significantly decreased and recovered when hemodialysis finished. (4) HH and HLMWH: gbACT were significantly increased and CR were rapidly decreased at both the arterial circuit and venous circuit at 2 h of hemodialysis. Low-dose heparin was effective and safe as anticoagulant in hemodialysis. Low-dose low-molecular-weight heparin was efficient in anticoagulation to some extent. However, High-dose low-molecular-weight heparin, high-dose heparin and flushing with heparinized saline may increase the risk of hemorrhage.

Clinical and biomaterial evaluation of hyaluronan-based heparin-bonded extracorporeal circuits with reduced versus full systemic anticoagulation in reoperation for coronary revascularization

This prospective randomized study compares full and reduced heparinization on novel hyaluronan-based heparin-bonded circuits vs. uncoated controls under challenging clinical setting including biomaterial evaluation. 100 patients undergoing reoperation for coronary artery bypass grafting were allocated into two equal groups (n = 50): Group one was treated with hyaluronan-based heparin bonded preconnected circuits (Vision HFOGBS, Gish, California, USA) and Group two with identical uncoated controls (Vision HFO, Gish, USA). In the study group, half of the patients (n = 25) received low-systemic heparin (125 IU/kg, ACT >250 s) or full dose like control group. Blood samples were collected after induction of anesthesia (T1) and heparin administration before cardiopulmonary bypass (CPB) (T2), 15 min after initiation of CPB (T3), before cessation of CPB (T4), 15 min after reversal with protamine (T5), and the first postoperative day at 08: 00 h (T6). Platelet counts were preserved significantly better at T5, T6 in hyaluronan groups (P < 0.05 vs. control). Serum IL-2 levels were significantly lower at T4, T5 in both hyaluronan groups and C3a levels at T4 and T5 only in low-dose group (P < 0.05). Troponin-T levels in coronary sinus blood demonstrated well preserved myocardium in hyaluronan groups. No significant differences in thrombin-antithrombin levels were observed between full and low-dose heparin groups at any time point. Amount of desorbed protein was 1.41 +/- 0.01 in full and 1.43 +/- 0.01 in low dose vs. 1.78 +/- 0.01 mg/dl in control (P < 0.05). Hyaluronan-based heparin-bonded circuits provided better clinical outcome and less inflammatory response compared with uncoated surfaces. Reduced systemic heparinization combined with hyaluronan-based heparin-bonded circuits is feasible and clinically well tolerated.

Coagulation effects of low molecular weight heparin compared with heparin in dogs considered to be at risk for clinically significant venous thrombosis

Compare the effects of 3 anticoagulation protocols on anti-factor Xa activity (AXa). Prospective, randomized, double-blind study. University veterinary teaching hospital. Eighteen dogs considered to be at risk for venous thrombosis. Each dog was randomly assigned to 1 of the following 3 groups (n=6/group) and was treated for 24 hours: low-dose heparin (LDH), high-dose heparin (HDH), and dalteparin (DP). Dogs in the LDH group received a constant rate infusion (CRI) of unfractionated heparin (UFH) at 300 U/kg/d, the HDH group received a bolus of 100 U/kg of UFH IV, then a CRI of 900 U/kg/day, and the DP group received 100 U/kg DP SC at 0, 12, and 24 hours. A total of 54 samples for activated partial thromboplastin time (aPTT) and AXa assays were collected at 0, 4, and 28 hours. Six samples had an AXa >0.1 U/mL, 5 of those were from the HDH group at hour 4. Two samples from the HDH group at hour 4 had a prolonged aPTT (93 and 200 seconds) and the highest AXa (0.6 and 1.0 U/mL, respectively). Four additional dogs in the HDH group did not complete the study due to hemorrhage; none of the dogs completing the study showed signs of hemorrhage. Neither DP nor LDH increased AXa to values considered therapeutic in humans (0.5-1 and 0.35-0.75 U/mL, respectively), and both protocols appear to be inadequate to increase AXa in dogs with clinical illness. HDH increased AXa to this range in 2 of 6 dogs, but had unpredictable effects on aPTT and resulted in hemorrhage in some dogs.

Continuous venovenous hemofiltration without anticoagulation.

We conducted a prospective observational study to assess the efficacy of continuous venovenous hemofiltration (CVVH) with no anticoagulation. A standard anticoagulation protocol for CVVH, which prescribed no anticoagulation for patients at risk of bleeding, was applied to 48 critically ill patients treated with CVVH. Circuit life was prospectively observed, and the following data were obtained for each circuit: heparin use and dose, protamine use, daily prothrombin time-international normalized ratio, activated partial thromboplastin time, and platelet count. Out of 300 consecutive circuits, 143 (47.6%) received no anticoagulation, 31 (10.3%) received regional anticoagulation, and 126 received low dose heparin. No patients experienced bleeding complications secondary to CVVH. Platelet count was significantly lower in the no anticoagulation group (73 x 10(3)/microl) compared with the low dose heparin group (119 x 10(3)/microl) and the protamine group (104 x 10(3)/microl) (p < 0.01 for both comparisons). There was no significant difference in mean circuit life among the three groups (heparin, 20.9 hours; no anticoagulation, 19.3 hours; protamine, 21.2 hours; not significant). In conclusion, for a group of patients deemed to be at risk of bleeding, CVVH without anticoagulation achieved an acceptable circuit life, which was similar to that obtained in other patients with low dose heparin anticoagulation or regional anticoagulation with heparin/protamine.

Surgical results of low-dose systemic heparinization (1 mg/kg, 100 IU/kg) in thoracic aortic operation combined with a heparin-coated cardiopulmonary bypass circuit: Is low-dose heparinization safe during deep hypothermic circulatory arrest?

Heparin-coated cardiopulmonary bypass circuits allow a reduction in the use of systemic heparin administered during cardiopulmonary bypass. This study was carried out to investigate safety during deep hypothermic circulatory arrest in this low-dose heparin group during thoracic aortic operation. Heparin-coated cardiopulmonary bypass circuits were used in 30 adult patients who underwent thoracic aortic operations that required deep hypothermic circulatory arrest. The patients were divided into two groups. Six patients received 300 IU/kg of heparin, and the remaining 24 patients received 100 IU/kg. Clinical outcomes (mortality, incidence of stroke, and transfusion volumes during operation) were examined. All devices remained functional throughout the procedures, and no systemic emboli were detected. Two deaths occurred in the high-dose heparin group, but no deaths occurred in the low-dose heparin group (P = 0.03). The percentage of patients requiring transfusion was similar in the two groups (66.7% vs. 70.8%), but the median exposure to allogenic blood products was greater in the high-dose heparin group than in the low-dose heparin group (9.8 ± 9.5 units vs. 5.5 ± 5.2 units; P = 0.09). Reduced systemic heparinization, combined with hepar-in-coated cardiopulmonary bypass circuits during deep hypothermic circulatory arrest, can be performed with acceptably low early mortality in thoracic aortic operations. Patients are not at increased risk for stroke.

Breast 07

Background: There is evidence that the heparins may affect tumour growth. We examined the effects of heparin and low molecular weight heparins in breast and colon cancer. Methods: • Experiment 1. Human colon cell lines SW 480, 620 and 707, and breast cancer cell lines 4T1 and MDA were incubated with medium alone, heparin, enoxaparin or tinzaparin, correlating with prophylactic to therapeutic doses. Tumour cell proliferation was assessed. • Experiment 2. Balb/c mice were inoculated with 4T1 cells intravenously, and received control, heparin, enoxaparin or tinzaparin at low and high doses subcutaneously daily. Animals were killed on day 12 and the lung:body weight ratio and metastatic score were calculated. Results: • Experiment 1. High-dose tinzaparin (33.4 per cent ± 13.1) inhibited breast tumour cell proliferation when compared to enoxaparin (65.4 per cent ± 14.1) or heparin (97.6 per cent ± 12.9) (P < 0.004). High-dose heparin (52.9 per cent ± 18.1) inhibited colon tumour cell proliferation significantly greater than either enoxaparin (110.2 per cent ± 31.9) or tinzaparin (125.9 per cent ± 13.1) (P = 0.003). • Experiment 2. Tumour growth was less in the low-dose tinzaparin group compared to the low-dose heparin group (lung : body weight ratio = 0.008 and 0.01, respectively; P = 0.02). Tumour growth was less in the high-dose tinzaparin group compared to the high-dose enoxaparin group (lung : body weight ratio = 0.008 and 0.01, respectively; P = 0.02; metastatic score = 2.6 and 3.9, respectively; P = 0.02). Conclusions: These results indicate that tinzaparin may be the anticoagulant of choice in patients with neoplastic disease in prophylactic or therapeutic settings.

Glycoprotein Iib/Iiia Receptor Antagonists: A Review of the Pivotal Trials

A statistically significant reduction in the composite endpoint was seen for patients who received the abciximab bolus plus infusion vs those who received a placebo (P = 0.008). This benefit was maintained at 6 months and at 3 years. Also noteworthy in this trial was the increased number of bleeding complications experienced by patients who received the abciximab bolus plus infusion regimen. Heparin dosing was quite liberal in this study, and infusions continued for at least 12 hours (1). The 2792 patients included in the EPILOG study were undergoing elective or urgent revascularization procedures. Patients could be at all risk levels, but those with UA or acute MI were excluded. Heparin dosing was adjusted for weight, which was not done in the EPIC trial. The primary endpoints for this study were death from any cause, MI or reinfarction, or severe MI requiring urgent CABG or repeat revascularization within 30 days. After the first interim analysis, statistical significance was reached between the responses of the abciximab plus low-dose heparin group vs the placebo group, and patient enrollment was therefore terminated. Patients in the placebo group had a higher rate of endpoint events (P < 0.001). The incidence of bleeding was not higher for patients receiving abciximab plus heparin therapy (2). The CAPTURE study was designed to evaluate patients with refractory UA. The primary endpoints were defined as death, MI, or the need for an urgent procedure to treat a recurrent ischemic episode. In contrast to the previously described abciximab studies, infusions were started 18 to 24 hours before the start of the scheduled angioplasty procedure and were continued for 1 hour afterwards. The study was discontinued prematurely, after 1265 patients were enrolled. At the third interim analysis, a statistically significant higher percentage of patients in the placebo group had reached the primary endpoint compared with those in the abciximab group (P = 0.0064) (3). The final abciximab study is the EPISTENT trial. Previous work had established that stenting was superior to balloon angioplasty because stenting reduced the need for repeat revascularization. Despite this technological advancement, the rates of death and MI had not decreased proportionately. The other

High dose heparin as pretreatment for primary angioplasty in acute myocardial infarction: the Heparin in Early Patency (HEAP) randomized trial

OBJECTIVESIn the Heparin in Early Patency (HEAP) pilot study a beneficial effect of high-dose heparin on early patency in acute myocardial infarction (MI) was observed in a matched-control study.BACKGROUNDHigh dose bolus intravenous injection of heparin may achieve lysis of coronary thrombi and could enhance early patency of the infarct related vessel in patients with MI scheduled for primary angioplasty.METHODSBefore primary angioplasty, 584 patients with MI entered an open randomized trial of high dose (300 IU/kg) or low dose (0 or 5,000 IU) heparin. Of the 584 patients, 299 were randomized to high dose and 285 patients to low dose heparin.RESULTSThrombolysis In Myocardial Infarction (TIMI) flow grade 2 or 3 was observed before primary angioplasty in 65 patients (22%) in the high dose group and 60 patients (21%) in the low dose heparin group (p > 0.1), whereas TIMI flow grade 3 was observed in 38 (13%) and 24 patients (9%), respectively (p = 0.11). There were no differences in the clinical end points between the two groups. There were no hemorraghic strokes, while 10% of the patients in the high dose group required blood transfusion versus 6% in the low dose/no heparin group (p = 0.07). No subsets of patients showed beneficial effects of high dose heparin, such as patients with longer delay between heparin administration and diagnostic angiogram or patients with short delay between symptom onset and admission.CONCLUSIONSThere is no benefit of high dose bolus heparin on early patency compared with no or low dose heparin.

Anticoagulants and hematomas in free flap surgery.

A review of systemic anticoagulant use in 517 free flap procedures was performed to determine the associated risk of hematoma formation. Patients were divided retrospectively (not randomly) into five groups: no anticoagulation (227 flaps, 5.3 percent hematomas), low-dose heparin bolus of 2000 to 3000 units and postoperative infusion at a rate of 100 to 400 units/hr for 5 to 7 days (192 flaps, 6.7 percent hematomas), intraoperative bolus of 5000 units of heparin without postoperative anticoagulation (46 flaps, 6.5 percent hematomas), high-dose heparin infusion at a rate of 500 to 1200 units/hr (30 flaps, 20 percent hematomas), and dextran 40 infusion at a rate of 25 ml/hr (22 flaps, 9.1 percent hematomas). Intraoperative blood loss was similar for all groups. The flap loss rate was lower in the bolus (1.0 percent) and low-dose (1.0 percent) heparin groups than in the no-anticoagulation group (4.4 percent), but this difference was not statistically significant. The pedicle thrombosis rate also was lower in the bolus (2.2 percent) and low-dose (2.1 percent) heparin groups than in the no-anticoagulation group (6.2 percent). A cause-and-effect relationship between the use of anticoagulants and flap loss or prevention of thrombosis could not be established. We can conclude, however, that the use of low-dose heparin does not increase significantly the risk of hematoma or intraoperative bleeding.

Calcium homeostasis in pregnancy during long-term heparin treatment.

To investigate the effect of subcutaneous heparin treatment on calcium homeostasis in pregnancy. A longitudinal case-control observational study. Department of Obstetrics and Gynaecology, Karolinska Hospital, Stockholm, Sweden. 36 pregnant women with previously verified thromboembolic complications and 23 healthy pregnant control women similar in age, parity, weight, and smoking habit. Thromboprophylaxis during pregnancy and 6 weeks post partum was given with subcutaneous heparin twice daily to the 36 women with a history of thromboembolic complications, 16 received an average dose of 24,500 IU/day and 20 a mean dose of 17,300 IU/day. Venous blood and urine samples were obtained every 4 weeks. Serum concentrations of total calcium, ionized calcium, calcitonin and urinary calcium. Women on high-dose heparin treatment showed significantly higher concentrations of total and ionized calcium and of calcitonin in serum and significantly lower concentrations of calcium in urine than did 23 normal pregnant controls. The differences were most pronounced in the third trimester. The results obtained in the low-dose heparin group were between those in the high-dose and the control groups. At 8 weeks postpartum there were no significant differences between the heparin-treated women and the controls. No significant differences were found during pregnancy in haematocrit, liver or renal function, serum levels of albumin, phosphate, magnesium, alkaline phosphatase, parathyroid hormone or urinary cyclic AMP. Heparin treatment during pregnancy results in changes in calcium homeostasis and a dose-dependent response is suggested.

Thromboembolism Following Multiple Trauma

The true incidence of thromboembolic complications following multiple trauma is unknown, and no method of prophylaxis has been shown to be both safe and effective in managing seriously injured patients. In this prospective study, 113 trauma patients were assigned on admission to receive either low-dose heparin (LDH), (5,000 U subcutaneously every 12 hours) or to wear sequential compression devices (SCDs) as prophylaxis against the development of deep venous thrombosis (DVT). Both groups of patients were serially studied with duplex venous ultrasound imaging to detect thrombus in the veins of the thigh. Ventilation-perfusion lung scans and pulmonary angiograms were performed when pulmonary embolism (PE) was suspected clinically. There were 12 patients who had thromboembolic complications, including 9 of 76 in the SCD group (12%) and 3 of 37 in the LDH group (8%). Five patients had DVT only, four had PE without detectable DVT, and three had both DVT and PE. None of the patients with PE died, and there were no major complications associated with either method of prophylaxis. Compared with the patients who did not develop DVT/PE, those with thromboembolic complications were older (49 +/- 23 vs. 36 +/- 17 years, p less than 0.02), spent more hospital days immobilized (24 +/- 15 vs. 10 +/- 13 days, p less than 0.001), received more transfusions (11 +/- 12 vs. 3 +/- 5 U, p less than 0.001) and had clotting abnormalities on admission, as demonstrated by prolonged PTT values (39 +/- 28 vs. 26 +/- 5 seconds, p less than 0.001). It appears that there is an identifiable subgroup of injured patients at highest risk for PE who warrant both prophylaxis and close surveillance for DVT.

Low Molecular Weight Heparin and Prevention of Postoperative Thrombosis in Abdominal Surgery

In a prospective, double-blind, randomized multicenter trial the efficacy and safety of low molecular weight heparin and unfractionated heparin were compared for the prevention of postoperative deep vein thrombosis in patients undergoing abdominal surgery. Six hundred and seventy-three patients were randomly allocated to the two prophylaxis groups; 20 of these, however, did not undergo surgery and did not receive any prophylaxis. Of the remaining 653 patients 323 received one subcutaneous injection of 3,000 anti-Xa units of low molecular weight heparin and 330 received subcutaneously 5,000 U heparin three times a day. Treatment was initiated 2 h preoperatively and continued for 7 to 10 days. The occurrence of DVT was determined by the 125I-labelled fibrinogen uptake test and phlebography. Venous thrombosis was diagnosed in 24 of 323 patients (7.4%) treated with low molecular weight heparin and in 26 of 330 patients (7.9%) treated with low-dose heparin. DVT of proximal veins was detected in four patients of the low molecular weight heparin group and in three patients of the low-dose heparin group. During the observation period three pulmonary emboli - one fatal and two non-fatal - occurred in patients receiving prophylaxis with low-dose heparin. No pulmonary embolism was found in patients treated with low molecular weight heparin. Both prophylactic schemes were well tolerated. Intra- and postoperative blood loss, incidence of wound hematoma, frequency and volume of intra- and postoperative blood transfusion were similar in both groups with a slight advantage for the low molecular weight heparin group.(ABSTRACT TRUNCATED AT 250 WORDS)

Venous thromboembolism prophylaxis in gynecologic oncology: A prospective, controlled trial of low-dose heparin

One hundred eighty-five patients undergoing operation-for gynecologic malignancy participated in a randomized controlled trial of low-dose heparin prophylaxis. Prospective surveillance for deep venous thrombosis was performed with daily fibrinogen 125I counting in the legs and impedance plethysmography. Twelve of 97 (12.4%) patients in the control group and 13 of 88 (14.8%) patients in the low-dose heparin group developed a venous thromboembolic complication. There was no statistical difference in the incidence of proximal deep vein thrombosis, calf vein thrombosis, or pulmonary emboli between the control and low-dose heparin groups. Low-dose heparin does not afford any prophylactic benefit to patients undergoing major pelvic operative procedures for gynecologic malignancy.