heparitin-sulfate and Postoperative-Complications

Heparin induced thrombocytopenia (HIT) in addition to bleeding complications are the most serious and dangerous side effects of heparin treatment. HIT remains the most common antibody-mediated, drug-induced thrombocytopenic disorder and a leading cause of morbidity and mortality. Two types of HIT are described: Type I is a transitory, slight and asymptomatic reduction of platelet count occurring during 1-2 days of therapy. HIT type II, which has an immunologic origin, is characterized by a thrombocytopenia that generally onset after the fifth day of therapy. Despite thrombocytopenia, haemorrhagic complications are very rare and HIT type II is characterized by thromboembolic complications consisting in venous and arterial thrombosis. The aim of this paper is to review new aspects of epidemiology, pathophysiology, clinical features, diagnosis and therapy of HIT type II. There is increasing evidence that platelet factor 4 (PF4) displaced from endothelial cells, heparan sulphate or directly from the platelets, binds to heparin molecule to form an immunogenic complex. The anti-heparin/PF4 IgG immune-complexes activates platelets through binding with the Fcgamma RIIa (CD32) receptor inducing endothelial lesions with thrombocytopenia and thrombosis. Cytokines are generated during this process and inflammation could play an additional role in the pathogenesis of thromboembolic manifestations. The onset of HIT type II is independent from dosage, schedule, and route of administration of heparin. A platelet count must be carried out prior to heparin therapy. Starting from the fourth day, platelet count must be carried out daily or every two days for at least 20 days of any heparin therapy regardless of the route of the drug administration. Patients undergoing orthopaedic or cardiac surgery are at higher risk for HIT type II. The diagnosis of HIT type II should be formulated on basis of clinical criteria and confirmed by in vitro demonstration of heparin-dependent antibodies detected by functional and antigen methods. However, the introduction of sensitive ELISA tests to measure anti-heparin/PF4 antibodies has showed the immuno-conversion in an higher number of patients treated with heparin such as the incidence of anti-heparin/PF4 exceeds the incidence of the disease. If HIT type II is likely, heparin must be immediately discontinued, even in absence of certain diagnosis of HIT type II, and an alternative anticoagulant therapy must be started followed by oral dicuma

Topics: Animals; Anticoagulants; Arginine; Chondroitin Sulfates; Dermatan Sulfate; Heparin; Heparitin Sulfate; Hirudins; Humans; Peptide Fragments; Pipecolic Acids; Postoperative Complications; Recombinant Proteins; Sulfonamides; Thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is an antibody-mediated syndrome associated with heparin exposure, a falling platelet count and a high risk of thrombosis. Cardiovascular patients are at increased risk of HIT due to wide use of heparin in this population. Should HIT be suspected, heparin must be avoided in most situations, and anticoagulation with an alternative anticoagulant should be instituted. Preferred agents include the direct thrombin inhibitors argatroban and lepirudin, whilst bivalirudin or desirudin (other direct thrombin inhibitors) can be used in some situations. The indirect thrombin inhibitors, danaparoid and fondaparinux, can also be considered at times. These agents and their use in cardiac patients, including patients with acute coronary syndrome, percutaneous coronary interventions, acute ST elevation myocardial infarction or cardiac surgery, will be reviewed.

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Arginine; Cardiovascular Diseases; Chondroitin Sulfates; Dermatan Sulfate; Drug Administration Schedule; Factor Xa Inhibitors; Fondaparinux; Heparin; Heparitin Sulfate; Hirudins; Humans; Pipecolic Acids; Polysaccharides; Postoperative Complications; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Recombinant Proteins; Sulfonamides; Thrombin; Thrombocytopenia

All patients with neurologic diseases should receive perioperative VTE prophylaxis. The choice of mechanical, pharmacologic, or combined modalities of prophylaxis depends on both the underlying risk factors and surgical VTE risks. Prophylaxis and treatment options must be individualized to the patient. Prevention of VTE will help minimize the need for therapeutic treatment. Options for treatment include both inpatient and outpatient regimens using UFH or LMWH. In patients with an absolute or relative contraindication to anticoagulation, an IVC filter is an appropriate management strategy. Perioperative bridging therapy should be considered in patients with high or moderate risks for recurrent VTE.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Aspirin; Brain Diseases; Chondroitin Sulfates; Dermatan Sulfate; Dose-Response Relationship, Drug; Drug Combinations; Fibrinolytic Agents; Heparin; Heparitin Sulfate; Humans; Postoperative Complications; Venous Thrombosis; Warfarin

In the absence of prophylaxis, elective orthopedic surgery is associated with a high risk of venous thromboembolic events that are responsible for substantial morbidity and mortality. Despite the publication of articles questioning the significance of fatal pulmonary embolism (PE) following elective hip replacement, recent reports support the need for effective thromboprophylaxis in this indication. These reports also provide evidence of a significant reduction in fatal PE and overall mortality provided by treatment with low-molecular-weight heparin (LMWH), compared with unfractionated heparin. Even with the most effective prophylaxis currently available, however, deep vein thrombosis still develops in a minority of high-risk patients, indicating a need for improved therapies. Desirudin, a novel recombinant hirudin and direct thrombin inhibitor, has been shown to provide more effective prophylaxis than the most widely used LMWH, enoxaparin, in orthopedic surgery patients with multiple thromboembolic risk factors. This benefit was not associated with any increase in bleeding. Regional anesthesia and use of graduated compression stockings may provide additional independent reductions in thromboembolic risk in elective orthopedic surgery.

Topics: Anesthesia, Conduction; Anticoagulants; Bandages; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Heparin, Low-Molecular-Weight; Heparitin Sulfate; Hirudin Therapy; Hirudins; Humans; Logistic Models; Postoperative Complications; Pulmonary Embolism; Recombinant Proteins; Risk Factors; Venous Thrombosis

Besides low molecular weight heparins (LMWHs) a number of new antithrombotic agents have been evaluated mainly in the prevention of deep vein thrombosis (DVT) and, to a lesser extent, in the treatment of established DVT. They include the Pentasaccharide, a synthetic ultra LMWH, Dermatan Sulphate, a glycosaminoglycan which activates heparin cofactor II, Orgaran, a mixture of Heparan and of Dermatan Sulphate, Hirulog and Hirudin, two direct thrombin inhibitors. The efficacy and safety of these compounds have been studied in comparison with a placebo or with unfractionated heparin but not with LMWH which is considered as a gold standard for these clinical indications. It is thus difficult at present to appreciate the advantages of these new antithrombotic agents over conventional LMWH therapy.

Topics: Anticoagulants; Antithrombin III; Binding Sites; Chondroitin Sulfates; Clinical Trials as Topic; Dermatan Sulfate; Drug Evaluation, Preclinical; Factor Xa Inhibitors; Fibrinolytic Agents; Heparin; Heparin, Low-Molecular-Weight; Heparitin Sulfate; Humans; Multicenter Studies as Topic; Oligosaccharides; Postoperative Complications; Pulmonary Embolism; Recurrence; Thrombin; Thrombophlebitis

On the basis of the results of the 11 studies reviewed, thromboprophylaxis with unfractionated heparin, low molecular weight (LMW) heparin or a heparinoid (danaparoid sodium; Org 10172) in patients undergoing total hip replacement did not show any important clinical differences with respect to the tolerability profiles of the different compounds. However, as a result of the great variability in the presentation and evaluation of blood losses and bleeding complications in these studies, it is mandatory to perform a direct comparison of the different compounds in question in a double-blind, prospective clinical study.

Topics: Chondroitin Sulfates; Dermatan Sulfate; Fibrinolytic Agents; Hemorrhage; Heparin; Heparinoids; Heparitin Sulfate; Hip Prosthesis; Humans; Molecular Weight; Postoperative Complications; Thrombocytopenia; Thrombosis; Wound Infection

Topics: Animals; Anticoagulants; Blood Coagulation; Cerebrovascular Disorders; Chondroitin Sulfates; Dermatan Sulfate; Drug Evaluation, Preclinical; Fibrinolytic Agents; Glycosaminoglycans; Hemorrhage; Heparin; Heparitin Sulfate; Humans; Incidence; Mammals; Molecular Weight; Platelet Aggregation; Postoperative Complications; Rabbits; Renal Dialysis; Thrombocytopenia; Thrombophlebitis; Thrombosis

Topics: Animals; Cardiopulmonary Bypass; Chondroitin Sulfates; Clinical Trials as Topic; Dermatan Sulfate; Factor X; Factor Xa; Fibrinolytic Agents; Glycosaminoglycans; Heparin; Heparinoids; Heparitin Sulfate; Humans; Kinetics; Molecular Weight; Postoperative Complications; Rats; Renal Dialysis; Thrombocytopenia; Thrombosis; Uremia

Preoperative administration of methylprednisolone reduced circulating markers of endothelial activation. This randomized, double-blind, placebo-controlled trial was to evaluate whether a single preoperative dose of methylprednisolone reduced the rate of postoperative delirium (POD) in older patients undergoing gastrointestinal surgery and its association with the shedding of endothelial glycocalyx markers.. About 168 patients, aged 65-80 years and scheduled for laparoscopic gastrointestinal surgery, were randomized to 2 mg/kg methylprednisolone (Group M, n = 84) or equivalent dose of placebo (Group C, n = 84). The primary outcome was the incidence of delirium during the first 5 days after surgery, assessed by the Confusion Assessment Method (CAM). POD severity was rated daily using CAM-Severity (CAM-S). Levels of syndecan-1, heparan sulfate, tumor necrosis factor-α (TNF-α), and brain-derived neurotrophic factor (BDNF) were measured at baseline, 1 day, and 3 days after surgery.. Compared with placebo, methylprednisolone greatly reduced the incidence of delirium at 72 hours following surgery (9 [10.7%] vs 20 [23.8%], p = .03, OR = 2.22 [95% CI 1.05-4.59]). No between-group difference was found in the cumulative CAM-S score (p = .14). The levels of heparan sulfate, syndecan-1, and TNF-α in Group M were lower than that in Group C (p < .05 and p < .01), while the level of BDNF in Group M was higher than that in Group C (p < .01).. Preoperative administration of methylprednisolone does not reduce the severity of POD, but may reduce the incidence of delirium after gastrointestinal surgery in older patients, which may be related to a reduction in circulating markers of endothelial degradation, followed by the increase of BDNF level.. Chinese Clinical Trial.gov, ChiCTR2000028792. Registered January 4, 2020. http://www.chictr.org.cn/showproj.aspx?proj=47807.

Topics: Aged; Brain-Derived Neurotrophic Factor; Delirium; Digestive System Surgical Procedures; Double-Blind Method; Heparitin Sulfate; Humans; Methylprednisolone; Postoperative Complications; Syndecan-1; Tumor Necrosis Factor-alpha

Topics: Aged; Aged, 80 and over; Anesthesia; Anesthesia, General; Chemoprevention; China; Female; Heart Rate; Heparitin Sulfate; Hospitalization; Humans; Hyaluronic Acid; Incidence; Intraoperative Period; Length of Stay; Lumbar Vertebrae; Male; Middle Aged; Norepinephrine; Postoperative Complications; Prospective Studies; Regression Analysis; Spinal Fusion; Spine; Syndecan-1

The endothelial glycocalyx, a carbohydrate-rich layer coating all endothelial surfaces, plays a fundamental role in the function of microcirculation. The primary aim of this study was to evaluate the feasibility of using dexamethasone and albumin to protect the endothelial glycocalyx in patients undergoing abdominal surgery. Secondary and exploratory outcomes included efficacy and safety.. We conducted a multicenter, open-label, blinded end point, phase 2, randomized trial. Patients undergoing colorectal, pancreas, or liver surgery were recruited and randomized to receive either intravenous dexamethasone (16 mg) and 20% albumin (100 mL) at induction of anesthesia, then 200 mL of 20% albumin with each subsequent 1000 mL of crystalloid administered (dexamethasone and albumin [Dex-Alb] group), or crystalloid fluid only with no dexamethasone (control group). Feasibility end points included patient recruitment and retention, consent rate, and successful study drug administration. The primary efficacy end point was the measurement of plasma syndecan-1 level on postoperative day (POD) 1, and secondary end points were heparan sulfate levels and inflammatory markers measured at 4 perioperative timepoints. Safety end points included errors in administration of the intervention, hyperglycemia, occurrence of postoperative complications, and patient retention.. Seventy-two patients were randomized. All feasibility end points were achievable. There were no statistically significant differences observed in median (interquartile range) syndecan-1 levels on POD 1 (39 ng·mL-1 [20-97] in the Dex-Alb group versus 41 ng·mL-1 [19-84] in the control group; difference in medians -2.1, 95% confidence interval [CI], -13 to 8.6; P = .69). The Dex-Alb group had lower POD 1 heparan sulfate levels (319 ng·mL-1 [161-717] in the Dex-Alb group versus 1422 [670-2430] ng·mL-1 in the control group; difference in medians -1085, 95% CI, -1779 to -391) and C-reactive protein (CRP) levels on POD 1 (48 [29-77] mg·L-1 in the Dex-Alb group versus 85 mg·L-1 [49-133] in the control group; difference in medians -48, 95% CI, -75 to -21). Fewer patients had one or more postoperative complication in the Dex-Alb group than in the control group (6 [17%] vs 18 patients [50%]; odds ratio = 0.2, 95% CI, 0.06-0.6).. Intravenous dexamethasone and albumin administration was feasible but did not reduce syndecan-1 on POD 1 in patients undergoing abdominal surgery. Given the clinically important CIs observed between the groups for heparan sulfate, CRP, and postoperative complications, a larger trial assessing the associations between dexamethasone and albumin administration and these outcomes is warranted.

Topics: Abdomen; Aged; Albumins; Biomarkers; C-Reactive Protein; Crystalloid Solutions; Dexamethasone; Digestive System Surgical Procedures; Endothelium, Vascular; Feasibility Studies; Female; Glucocorticoids; Glycocalyx; Heparitin Sulfate; Humans; Infusions, Intravenous; Male; Microvessels; Middle Aged; New Zealand; Postoperative Complications; Preoperative Care; Syndecan-1; Time Factors; Treatment Outcome; Victoria

Decreased antithrombin III (ATIII) activity and large splenic vein diameter (SVD) are risk factors for portal vein thrombosis (PVT) after splenectomy in liver cirrhosis with portal hypertension. Antithrombin III concentrates can prevent PVT. This study was designed to stratify risks for PVT after splenectomy in cirrhotic patients and to develop prophylactic protocols for PVT.. In 53 patients (testing cohort), the cutoff level of preoperative ATIII activity (≤60%) was evaluated for administration of ATIII concentrates. Antithrombin III activity and SVD were re-evaluated as criteria for prophylaxis of PVT. In 57 patients (validation cohort), the risk stratification of PVT and prophylactic protocols were validated.. In the testing cohort, 10 (19%) of 53 patients had PVT. Risk level of PVT was stratified and prophylactic protocols were developed. Patients at low risk (ATIII activity ≥70% and SVD <10 mm) were not treated; those at high risk (ATIII activity <70% or SVD ≥10 mm) received ATIII concentrates (1,500 U/day) for 3 days; and those at highest risk (SVD ≥15 mm) received ATIII concentrates for 3 days, followed by danaparoid sodium (2,500 U/day) for 14 days and warfarin. In the validation cohort, 0 of 14 low-risk and 2 of 32 high-risk patients had PVT. Although 8 of 11 patients at highest risk had temporary PVT, it disappeared within 3 months postoperatively. Finally, only 2 (3.5%) of 57 patients had PVT.. Risk stratification of PVT after splenectomy and prophylaxis with ATIII concentrates and danaparoid sodium dramatically reduced the incidence of PVT.

Topics: Adult; Aged; Anticoagulants; Antithrombin III; Chondroitin Sulfates; Clinical Protocols; Decision Support Techniques; Dermatan Sulfate; Drug Therapy, Combination; Female; Fibrinolytic Agents; Heparitin Sulfate; Humans; Hypertension, Portal; Laparoscopy; Liver Cirrhosis; Male; Middle Aged; Portal Vein; Postoperative Complications; Prospective Studies; Risk Assessment; Risk Factors; ROC Curve; Splenectomy; Venous Thrombosis; Warfarin

Orgaran (danaparoid sodium injection) is a novel antithrombotic agent. Early studies suggest that this compound may be beneficial in preventing deep vein thrombosis in predisposed patients. This multicenter, randomized, assessor blinded, clinical trial compared subcutaneous danaparoid with warfarin for the prevention of deep vein thrombosis in patients undergoing hip replacement surgery. Bilateral venography was used to detect thrombi. Patients also underwent follow-up examinations 1, 2, and 3 months after discontinuation of the study to determine the after effects of treatment. Nearly 27% of patients who received warfarin and 14.6% of patients who received danaparoid developed deep vein thrombosis, a risk reduction of 46%. The absolute difference in the incidence of deep vein thrombosis was 12.3% in favor of danaparoid. The incidence of venographically documented proximal deep vein thrombosis was 1.5% for danaparoid and 4.1% for warfarin. These results demonstrate that danaparoid is more effective than warfarin in preventing deep vein thrombosis following hip replacement surgery. The preoperative administration of danaparoid does not increase surgical blood loss compared with warfarin.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Hip; Blood Loss, Surgical; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Female; Heparitin Sulfate; Humans; Male; Middle Aged; Postoperative Complications; Single-Blind Method; Treatment Outcome; Venous Thrombosis; Warfarin

The study objective was to determine the relative efficacy and safety of a low-molecular-weight heparinoid (Orgaran) compared with aspirin for the prevention of postoperative venous thromboembolism in patients undergoing surgery for fractured hips. A double-blind, randomized, controlled trial was used to study 251 consecutive eligible and consenting patients undergoing surgery for hip fracture in seven participating hospitals.. Patients received either fixed-dose Orgaran by subcutaneous injection every 12 hours in a dose of 750 anti-Factor Xa units or aspirin 100 mg orally twice daily; both regimens were started 12 to 24 hours after surgery and continued for 14 days or until discharge, if sooner. All patients had postoperative 125I-fibrinogen leg scanning and impedance plethysmography. If the results of one or both tests were positive, then venography was performed. Otherwise, venography was done at day 14, or sooner if the patient was ready for discharge. Pulmonary embolism in symptomatic patients was diagnosed on the basis of a high probability perfusion/ventilation lung scan, a positive angiogram, or a clinically significant embolism detected at autopsy. Evaluable venograms were obtained in 90 of the 125 patients randomly assigned to receive Orgaran and in 87 of the 126 patients assigned to receive aspirin. Venous thromboembolism was detected in 25 (27.8%) patients in the Orgaran group and in 39 (44.3%) patients in the aspirin group. Thus, there was a relative risk reduction of 37% with Orgaran (P=.028; 95% confidence interval, 3.7% to 59.7%). Six (6.8%) of 88 patients in the Orgaran group and 12 (14.3%) of 84 patients in the aspirin group developed proximal deep vein thrombosis or pulmonary embolism, a relative risk reduction of 52% with Orgaran (P=.137; 95% confidence interval, -30.7% to 84.6%). Hemorrhagic complications occurred in 2 (1.6%) patients given Orgaran and 8 (6.4%) patients given aspirin (P=.10). There was one major bleed in the Orgaran group compared with four in the aspirin group.. This study demonstrates that Orgaran is significantly more efficacious than aspirin in preventing postoperative venous thromboembolism in patients undergoing surgery for fractured hips, with no evidence of any increase in hemorrhagic complications.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Aspirin; Chondroitin Sulfates; Dermatan Sulfate; Double-Blind Method; Female; Heparitin Sulfate; Hip Fractures; Humans; Injections, Subcutaneous; Male; Middle Aged; Postoperative Complications; Thromboembolism

This double-blind, randomised, multicentre trial in 513 patients having elective surgery for intra-abdominal or intrathoracic malignancy compared the efficacy and safety of venous thrombosis (VT) prophylaxis using 750 anti-factor Xa units of Orgaran (a mixture of low molecular weight heparinoids) given subcutaneously (sc) twice-daily with that of twice-daily injections of 5,000 units standard heparin. The main study endpoints were the development of postoperative VT detected by 125I-fibrinogen leg scanning, and the onset of clinically significant venous thromboembolism or bleeding. "Intent to treat" analysis showed a statistically non-significant trend towards less VT during Orgaran prophylaxis (10.4%) than after heparin (14.9%) and there was no difference in bleeding complications between the two study groups. Results remained similar if only patients who completed the intended course of therapy ("compliant patients") were analysed. Other trials have shown that Orgaran prevents VT after hip surgery and stroke. We now show it is also safe and effective in patients having major surgery for cancer.

Topics: Aged; Anticoagulants; Chondroitin Sulfates; Dermatan Sulfate; Double-Blind Method; Elective Surgical Procedures; Female; Gastrointestinal Neoplasms; Glycosaminoglycans; Hematologic Tests; Hemorrhage; Heparinoids; Heparitin Sulfate; Humans; Lung Neoplasms; Male; Middle Aged; Postoperative Complications; Pulmonary Embolism; Thrombophlebitis

Two studies evaluating the effect of Orgaran prophylaxis on the incidence of postoperative thrombosis in hip fracture surgery are reported. In one Scandinavian study, dextran was used in the comparative group, and in the US study, warfarin was used. In both, Orgaran was significantly more effective in reducing the frequency of deep vein thrombosis without producing an increase in bleeding complications or other side effects.

Topics: Aged; Aged, 80 and over; Chondroitin Sulfates; Dermatan Sulfate; Dextrans; Female; Glycosaminoglycans; Hemorrhage; Heparinoids; Heparitin Sulfate; Hip Fractures; Humans; Incidence; Male; Postoperative Complications; Pulmonary Embolism; Scandinavian and Nordic Countries; Single-Blind Method; Thrombophlebitis; United States; Warfarin

Patients who develop heparin-induced thrombocytopenia (HIT) frequently need further anticoagulation to treat an ongoing thromboembolic problem or to prevent one. Orgaran (Org 10172), a low-molecular-weight (LMW) glycosaminoglycuronan, has shown a low frequency (10%) of cross-reactivity in vitro with sera containing the HIT antibody, in contrast to the much higher frequency of cross-reactivity (approximately 80%) shown by the LMW heparins. This paper summarises the results of intravenous or subcutaneous Orgaran treatment in 57 of 67 Australian patients, in whom the diagnosis of HIT was reasonably confirmed by exclusion of other causes of thrombocytopenia and by objective tests. The presenting indications for Orgaran were: continuous venovenous haemofiltration and haemodialysis (n = 21), thrombo-embolism treatment (n = 23), thrombo-embolism prophylaxis (n = 10), and anticoagulation for coronary artery by-pass graft (n = 4), peripheral by-pass graft surgery and plasmapheresis (n = 1 each). The results showed Orgaran to be a safe, well-tolerated, effective (successful treatment in over 90% of patients) anticoagulant in patients with a high thrombotic and/or bleeding risk even if critically ill and requiring haemofiltration. The complete results of the world-wide study in 161 patients confirmed not only these clinical findings in the subgroup of 57 Australian patients, but also the low cross-reactivity (12%) of Orgaran with the HIT serum factor.

Topics: Antibody Specificity; Autoantibodies; Autoimmune Diseases; Chondroitin Sulfates; Cross Reactions; Dermatan Sulfate; Drug Evaluation; Glycosaminoglycans; Hemofiltration; Heparin; Heparinoids; Heparitin Sulfate; Humans; Postoperative Complications; Thrombocytopenia; Thromboembolism

The paper reports the results of a randomised study carried out on a pool of 100 patients undergoing surgery in order to assess the efficacy and tolerability of orally administered heparan sulfate versus heparin calcium in the prevention of postoperative deep-vein thrombosis. Despite the limits of oral administration, heparan sulfate is indicated in the pharmacological prevention of postoperative deep-vein thrombosis.

Topics: Administration, Oral; Drug Tolerance; Fibrinolytic Agents; Heparin; Heparitin Sulfate; Humans; Postoperative Complications; Surgical Procedures, Operative; Thrombophlebitis

In a randomized, prospective trial, a low-molecular-weight heparinoid (Org 10172 [Lomoparan]) was compared with warfarin for efficacy and safety in preventing deep-vein thrombosis in 263 patients who had an operatively treated fracture of the hip. One group of patients received Org 10172 in a dose of 750 units subcutaneously every twelve hours until the ninth postoperative day; on the seventh postoperative day, warfarin was added to the regimen. The other group received only warfarin. Both drugs were begun preoperatively, immediately after the admission evaluation. In the patients who received warfarin, the desired prothrombin time was one and one-half times the control level. Deep-vein thrombosis was detected by 125I-fibrinogen scanning and impedance plethysmography and was confirmed by phlebography and compression ultrasonography. Deep-vein thrombosis was found in nine (7 per cent) of the 132 patients who received Org 10172 and in twenty-eight (21 per cent) of the 131 patients who received warfarin (p less than 0.001). Adverse reactions were not significantly different in the two groups. Major bleeding complications occurred in eight patients in the Org-10172 group, only four of whom were receiving the drug at the time of bleeding, and in five patients who were receiving warfarin (not significant). There was no difference in intraoperative loss of blood or in requirements for transfusion. We concluded that the low-molecular-weight heparinoid Org 10172 is a safe, convenient, effective antithrombotic agent for the prevention of venous thrombosis after an operation for fracture of the hip.

Topics: Aged; Aged, 80 and over; Blood Loss, Surgical; Chondroitin Sulfates; Dermatan Sulfate; Female; Glycosaminoglycans; Heparinoids; Heparitin Sulfate; Hip Fractures; Humans; Iodine Radioisotopes; Male; Middle Aged; Molecular Weight; Plethysmography; Postoperative Complications; Prevalence; Prospective Studies; Risk Factors; Thrombophlebitis; Warfarin

Topics: Animals; Cardiopulmonary Bypass; Chondroitin Sulfates; Clinical Trials as Topic; Dermatan Sulfate; Factor X; Factor Xa; Fibrinolytic Agents; Glycosaminoglycans; Heparin; Heparinoids; Heparitin Sulfate; Humans; Kinetics; Molecular Weight; Postoperative Complications; Rats; Renal Dialysis; Thrombocytopenia; Thrombosis; Uremia

Heparin-induced thrombocytopenia (HIT) is a potentially life-threatening prothrombotic complication following heparin administration. We describe a patient, known with idiopathic dilating cardiomyopathy, presenting nine days after a biventricular ICD implantation with dyspnoea and thrombocytopenia. Thirteen days after administration of a single heparin flush during ICD implantation, the patient developed venous thrombosis in two extremities and pulmonary embolism caused by HIT. HIT is the development of thrombocytopenia, caused by IgG antibodies against complexes of platelet factor 4 and heparin, leading to platelet aggregation. HIT may be accompanied by thrombosis in 20-50% of patients and untreated mortality rates are high. Once HIT is suspected, heparin should be replaced by an alternative anti-factor Xa or anti-factor II therapy. Regardless of the low incidence of HIT, because of the widespread use of heparin and the potentially life-threatening course of HIT, all physicians should be aware of it.

Topics: Antibodies; Anticoagulants; Cardiomyopathy, Dilated; Chondroitin Sulfates; Defibrillators, Implantable; Dermatan Sulfate; Female; Follow-Up Studies; Heparin; Heparitin Sulfate; Humans; Immunoglobulin G; Middle Aged; Platelet Aggregation; Platelet Factor 4; Postoperative Complications; Pulmonary Embolism; Thrombocytopenia; Treatment Outcome; Venous Thromboembolism

Bone morphogenetic proteins (BMPs) are recognized for their ability to induce bone formation in vivo and in vitro. Their osteogenic and osteoinductive properties are tightly regulated by the secretion of specific BMP antagonists, which have been shown to physically bind and sometimes be blocked by the extracellular proteoglycan heparan sulphate side chains (from hereon referred to as HS). The purpose of this study was to investigate if local application of 5 µg of HS proteoglycan to a bone regenerate site in a mouse model of distraction osteogenesis (DO) can accelerate bone healing and affect the expression of key members of the BMP signaling pathway. DO was performed on the right tibia of 115 adult male wild-type mice. At mid-distraction (day 11), half the group was injected locally with 5 µg of HS, while the other half was injected with saline. The mice were sacrificed at 2 time-points: mid-consolidation (34 days) and full consolidation (51 days). The distracted tibial zone was then collected for analysis by μCT, radiology, biomechanical testing, immunohistochemistry, and histology. While μCT data showed no statistically significant difference in bone formation, the results of biomechanical testing in stiffness and ultimate force were significantly lower in the HS-injected bones at 51 days, compared to controls. Immunohistochemistry results also suggested a decrease in expression of several key members of the BMP signaling pathway at 34 days. Furthermore, wound dehiscence and infection rates were significantly elevated in the HS group compared to the controls, which resulted in a higher rate of euthanasia in the treatment group. Our findings demonstrate that exogenous application of 5 µg of HS in the distracted gap of a murine model had a negative impact on bone and wound healing.

Topics: Animals; Biomechanical Phenomena; Bone Morphogenetic Proteins; Down-Regulation; Heparitin Sulfate; Male; Mice; Mice, Inbred C57BL; Osteogenesis; Osteogenesis, Distraction; Postoperative Complications; Signal Transduction; Tibia; X-Ray Microtomography

Itching erythematous or eczematous plaques around injection sites are quite frequent side effects of heparin treatment and are clinical symptoms of a delayed-type hypersensitivity to heparins. In most cases, changing the subcutaneous therapy from unfractionated to low molecular weight heparin or treatment with heparinoids does not provide improvement, due to extensive cross-reactivity. Interestingly, it has been demonstrated that patients with delayed-type hypersensitivity to subcutaneously injected heparins tolerate intravenous application of heparin in controlled challenge tests. A patient with known delayed-type hypersensitivity to heparins received the heparinoid, danaparoid, subcutaneously for thrombosis prophylaxis after orthopedic surgery. After the first few injections, eczematous plaques developed; administration of the anticoagulant was continued and gradually resulted in generalized eczema despite treatment with topical and oral glucocorticoids. However, the patient required further anticoagulation. After discontinuation of subcutaneous injections and a switch to intravenous heparin, rapid improvement and clearing of skin lesions occurred. Therefore, in cases of delayed-type hypersensitivity to subcutaneously injected heparins, the switch from subcutaneous to intravenous heparin administration may be justified.

Topics: Aged; Anticoagulants; Chondroitin Sulfates; Dermatan Sulfate; Dermatitis, Allergic Contact; Eczema; Female; Heparin; Heparitin Sulfate; Humans; Immobilization; Infusions, Intravenous; Injections, Subcutaneous; Postoperative Care; Postoperative Complications; Thrombophilia; Venous Thrombosis

Heparin-induced thrombocytopenia (HIT) represents a serious side effect caused by an atypical immune response to platelet factor 4 leading to platelet activation and thrombin formation. These patients are at high risk of thromboembolism, with a rapid drop in platelet count between days 5 and 14 after the initiation of heparin treatment. In single cases, especially after major surgery, platelet count reduction might be absent or hidden by preceding thrombocytosis. Different clinical manifestations of HIT include unspecific skin reactions with potential necrosis at the site of heparin injection, mostly after the application of unfractionated heparin but also with low molecular weight heparin. In heparin-induced skin necrosis, administration of unfractionated or low molecular weight heparin is contraindicated and heparin therapy should be stopped immediately. Instead, an alternative anticoagulant in the form of a direct thrombin inhibitor such as argatroban, and respectively lepirudin, or danaparoid sodium must be administered. Due to frequent misinterpretations of heparin-induced unspecific skin reactions, especially in the absence of thrombocytopenia, we present two case reports which should increase the awareness of HIT's various clinical pictures.

Topics: Adult; Anticoagulants; Arginine; Chondroitin Sulfates; Dermatan Sulfate; Drug Eruptions; Female; Heparin; Heparin, Low-Molecular-Weight; Heparitin Sulfate; Hirudins; Humans; Male; Pipecolic Acids; Platelet Count; Platelet Factor 4; Postoperative Complications; Recombinant Proteins; Sulfonamides; Thrombocytopenia; Thrombosis; Time Factors

Type 2 heparin-induced thrombocytopenia is an uncommon but often fatal complication of heparin, frequently difficult to diagnose after cardiac surgery. In this series, we record the clinical presentation, temporal relationship, and treatment outcome of patients diagnosed with heparin-induced thrombocytopenia postoperatively.. Thirty-three consecutive patients (1.1%) with a diagnosis of heparin-induced thrombocytopenia established by a greater than 50% drop in platelet count with or without a thrombotic event and a positive platelet factor-4 assay were reviewed. We recorded the clinical presentation, the time to presentation, treatment, and outcome (thrombosis, mortality). Univariate analysis was performed on 13 preoperative, operative, and postoperative variables.. The cohort was at increased mortality risk as a result of age (69.4 years), reduced cardiac function (46.8%), nonbypass operations (57.6%), emergency surgery (21.2%), and implantation of three assist devices. The mean time to suspect heparin-induced thrombocytopenia postoperatively was 5.4 days, with 22 cases (66.6%) occurring within 5 days. All patients had previous (within 3 months) exposure to heparin, and 66.6% had ongoing treatment with heparin before surgery. Overall mortality was 33%; thrombotic complications occurred in 15 patients (45.5%), with a mortality of 7 (46.6%) despite immediate cessation of heparin and treatment with a nonheparin analog. Thrombocytopenia without thrombosis occurred in 18 patients (54.5%), but a subgroup of 5 patients with nonthrombotic complications accounted for the 4 (22.2%) deaths.. Heparin-induced thrombocytopenia after cardiac surgery is uncommon but may occur within 5 days of surgery, further complicating diagnosis and treatment. Thrombotic complications result in a high mortality despite treatment with a nonheparin analog, and a subgroup of patients with thrombocytopenia fared poorly.

Topics: Aged; Aged, 80 and over; Anticoagulants; Autoantibodies; Cardiac Surgical Procedures; Chondroitin Sulfates; Cohort Studies; Dermatan Sulfate; Diabetes Complications; Female; Gangrene; Heparin; Heparitin Sulfate; Hospital Mortality; Humans; Ischemia; Male; Middle Aged; Platelet Factor 4; Postoperative Complications; Postoperative Period; Retrospective Studies; Risk Factors; Thrombocytopenia; Thrombosis; Time Factors; Treatment Outcome

Topics: Anticoagulants; Cardiac Surgical Procedures; Chondroitin Sulfates; Contraindications; Dermatan Sulfate; Heparin; Heparitin Sulfate; Humans; Platelet Count; Platelet Factor 4; Postoperative Complications; Postoperative Period; Serotonin; Thrombocytopenia; Time Factors; Treatment Outcome

We report the case of 64-year-old female patient with pulmonary embolism and bilateral femoropopliteal deep vein thrombosis caused by heparin-induced thrombocytopenia type II (HIT II) resistant to danaparoid sodium and subsequently administered lepirudin in whom a single late plasmapheresis performed on day 6 of the initiation of treatment of HIT reversed the course of the disease, preventing its highly potential fatal outcome. Primarily administered lepirudin was not only ineffective but even led to further aggravation of the patient's clinical state and platelet count drop in the first stage of the HIT treatment. The improvement of the patient's clinical state was not achieved before therapeutic plasma exchange (TPE) had removed the greatest part of pathogenetic circulating substrate. Only after TPE, lepirudin, introduced again, led to the platelet count recovery. In the subsequent course of the treatment, lepirudin was combined with an overlapping oral anticoagulant. Previously positive heparin aggregation test and fast particle gel heparin-platelet factor 4 immunoassay were normalized as well as the patient's clinical status. Early plasmapheresis, administered within 4 days of the onset of thrombocytopenia in HIT, as a beneficial therapeutic measure in certain individual cases, is indisputable. However, our results do not concur with previously reported findings of the so far most comprehensive study on plasmapheresis performed in the management of HIT with thrombosis, discrediting late plasmapheresis administered 4 days after the onset of the disease not only as ineffective, but even as an aggravating factor. Our results suggest the possible beneficial impact of late plasmapheresis as a method that may reverse a prothrombotic process and lead to a fast improvement in the patient's platelet count, especially in cases initially resistant to thrombin inhibitors.

Topics: Arthroplasty, Replacement, Hip; Autoantibodies; Chondroitin Sulfates; Dermatan Sulfate; Drug Resistance; Female; Fibrinolytic Agents; Heparin; Heparitin Sulfate; Hip Fractures; Hirudins; Humans; Middle Aged; Partial Thromboplastin Time; Plasma; Plasmapheresis; Postoperative Complications; Pulmonary Embolism; Purpura, Thrombocytopenic, Idiopathic; Recombinant Proteins; Salvage Therapy; Thrombophilia; Time Factors

Patients with heparin-induced thrombocytopenia urgently requiring surgery with cardiopulmonary bypass (CPB) present a unique management challenge that must be addressed by the use of alternative anticoagulants. Although clinical success with the direct thrombin inhibitor hirudin has been reported, there is sparse information in the literature supporting the efficacy of this drug as an anti-thrombotic to prevent fibrin formation during CPB. In this report, we describe the efficacy of this drug to prevent thrombin-mediated fibrin formation during CPB.

Topics: Adult; Anticoagulants; Cardiopulmonary Bypass; Chondroitin Sulfates; Contraindications; Dermatan Sulfate; Endarterectomy; Fibrinolytic Agents; Fibrinopeptide A; Heparin; Heparitin Sulfate; Hirudins; Humans; Hypertension, Pulmonary; Hypothermia, Induced; Male; Peptide Fragments; Postoperative Complications; Prothrombin; Pulmonary Embolism; Purpura, Thrombocytopenic, Idiopathic; Recombinant Proteins; Thrombectomy; Thrombin; Thrombosis

In the past 10 years numerous reports of cases referring to complications and their outcome with heparin-induced thrombocytopenia type II (HIT II) have been published. Clinically these symptoms are manifested as a combination of arterial and venous thromboembolisms. Mostly affected are the vessels of the limbs, the abdomen, kidneys and coronary arteries. We present the most rare initial manifestations of cerebral symptoms with headache, nausea, change of character and generalised convulsion, which have found their origin in sinus vein thrombosis and the treatment with the heparinoid danaparoid.

Topics: Aged; Anticoagulants; Anticonvulsants; Blood Cell Count; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Heparin; Heparitin Sulfate; Humans; Male; Mental Disorders; Postoperative Complications; Seizures; Sinus Thrombosis, Intracranial; Thrombocytopenia; Tomography, X-Ray Computed

Thrombosis prophylaxis using heparins is mandatory in most trauma patients. However, heparins can induce heparin-induced thrombocytopenia (HIT), the most common and clinically important immune-mediated drug-dependent thrombocytopenia. Affected patients are at risk of developing new thromboembolic complications. HIT has to be considered if platelet counts decrease >50% between day 5-10 of heparin therapy that cannot be explained alternatively or if new thromboses occur in a sufficiently heparinised patient. Immediately changing the anticoagulant to danaparoid or lepirudin is most important. Proof of anti-platelet-factor-4/heparin antibodies secures the diagnosis, usually retrospectively. Diagnosis and therapy are demonstrated in a typical HIT patient. HIT usually occurs in the second week of heparin administration. Heparin-reexposure within 100 days can lead to HIT before day 5. For early recognition of HIT, platelet counts should be monitored regularly. Because of earlier discharge of patients to rehabilitation or outpatient care, the problem of HIT-diagnosis and therapy gains increasing relevance in these sectors.

Topics: Adult; Anticoagulants; Autoantibodies; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Fractures, Bone; Heparin; Heparitin Sulfate; Hirudins; Humans; Male; Multiple Trauma; Platelet Count; Platelet Factor 4; Postoperative Complications; Recombinant Proteins; Thrombocytopenia; Thromboembolism

Heparin-induced thrombocytopenia (HIT) has become more prevalent in today's cardiac setting and has resulted in the need for alternative anticoagulant therapies. Danaparoid sodium, one alternative to heparin, has been used in six cardiopulmonary bypass procedures in this hospital. This clinical experience has resulted in the progressive refinement of a protocol for the 'safe' clinical use of danaparoid sodium. Although there were six positive outcomes with the use of danaparoid sodium, alternatives must be explored in order to find the optimal anticoagulant for the treatment of HIT.

Topics: Adult; Aged; Anticoagulants; Cardiopulmonary Bypass; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Female; Hemorrhage; Heparin; Heparitin Sulfate; Humans; Male; Middle Aged; Postoperative Complications; Thrombocytopenia

Heparin-induced thrombocytopenia type II (HIT-II) is a serious complication in heparin treatment. Because of arterial and/or venous thromboembolism, HIT-II quite often takes a life-threatening course. This article describes the clinical course of seven trauma patients, who developed HIT-II during thromboembolism prophylaxis with unfractionated heparin (UFH, Heparin-Natrium-Nattermann, 250,000 I.E., Rhone-Poulenc Rorer GmbH), given subcutaneously. Thromboembolic complications occurred in 5 out of 7 cases (71.4%). One case took a fatal course (14.3%). UFH was replaced by Orgaran when HIT-II was suspected or diagnosed. There were no more complications. Thrombocyte count increased to normal values within 3 to 9 days. The importance of HIT-II in heparin therapy during in- and outpatient therapy is discussed with reference to the current literature.

Topics: Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Hip; Chondroitin Sulfates; Dermatan Sulfate; Female; Femoral Neck Fractures; Heparin; Heparitin Sulfate; Hip Fractures; Humans; Male; Middle Aged; Multiple Trauma; Osteoarthritis, Hip; Platelet Count; Postoperative Complications; Thrombocytopenia; Thromboembolism

Use of definite molecular weight heparan sulphate in a protocol for the prevention of deep venous thrombosis in the total joint replacement surgery. The authors propose a working protocol for the prevention of deep venous thrombosis in prosthetic orthopaedic surgery. It requires that integration of pharmacological, anaesthesiological, rheological and physiokinesitherapic measures, it has permitted a very good prevention of thromboembolic disease and it is well-tolerated and safe. The protocol requires: peripheral anaesthesia (sub-arachnoidal block), pre and post-operative pharmacological treatment with heparan-sulphate of a fixed molecular weight, haemodilution with maintenance of the haematocrit at no more than 30%, early physiokinesitherapy associated with the use of elastic stockings graduated tension. The fifty patients treated with this protocol were controlled during the pre-operative and post-operative stage and one month later and no thrombo-embolic complications resulted.

Topics: Aged; Bandages; Exercise Therapy; Female; Heparitin Sulfate; Hip Prosthesis; Humans; Knee Prosthesis; Male; Molecular Weight; Postoperative Complications; Thrombophlebitis

The 29-year-old, heroin-addicted patient received an aortic valve prosthesis (SJM) 10 years ago because of aortic valve stenosis III. One year after surgical treatment he refused to take Phenprocoumon and thus received no anticoagulation for 9 years. The patient was hospitalized due to cardial decompensation and thrombosis of the aortic valve prosthesis was diagnosed. Under heparinization, he developed heparin-induced thrombocytopenia type II, which disappeared after changing the medication to Danaparoid-Sodium. In order to avoid any further heparin exposure, we also carried out the surgical replacement of the aortic valve prosthesis under anticoagulation with Danaparoid-Sodium.

Topics: Adult; Aortic Valve Stenosis; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Heart Valve Prosthesis; Heparin; Heparitin Sulfate; Heroin Dependence; Humans; Male; Platelet Count; Postoperative Complications; Prosthesis Failure; Reoperation; Thrombocytopenia; Thrombosis

Postoperative hemorrhage remains a serious complication in cardiopulmonary bypass (CPB) surgery. In our study, alternative anticoagulation with a new low molecular weight (LMW) heparinoid (Org 10172) was compared with a standardized heparin regimen. A preliminary dose-finding study indicated the minimal effective heparinoid dose to be 260 anti-Xa U/kg body weight, which was comparable to the standardized heparin regime, as revealed by similar plasma anti-Xa values. The following randomized open pilot study in 12 mongrel dogs undergoing CPB showed the heparinoid to be as effective as heparin, with an additional advantageous decrease in postoperative blood loss in the Org 10172 group. Our randomized blind study in 16 mongrel dogs undergoing CPB was performed to confirm previous results. Both antithrombotic agents were effective in the prevention of clot formation within the extracorporeal circuit. Hematocrit values and erythrocyte and platelet counts showed no significant intergroup differences. Post-CPB leukocyte counts revealed a significantly more rapid increase in the group given heparinoid (P less than 0.05). In the group given heparin, the expected prolongations of both the thrombin time (TT) and activated partial thromboplastin time (APTT) were noted, whereas in the group given heparinoid, only a transient peak prolongation of the TT after dose administration was revealed, and no significant prolongation of the APTT. Mean anti-Xa plasma levels were similar during CPB, showing a rapid decrease in the group given heparin on protamine administration, as did the APTT. Assessment of the operating field indicated an elevated intraoperative blood loss in the group given heparin. Postoperative blood loss measured over a period of 2.5 hours after closure of the thorax was significantly lower in the group given heparinoid than in the heparinized animals (625 +/- 100.0 ml, mean +/- SD, and 806 +/- 178.2 ml, respectively; P less than 0.05). Our observations suggest that the LMW heparinoid Org 10172 has an increased benefit/risk ratio over standard heparin and is effective in CPB in dogs. Additional investigations in humans should verify the possibility of use of this substance as an alternative means of anticoagulation during CPB in patients in whom heparin is relatively contraindicated.

Topics: Animals; Antithrombins; Blood Coagulation Tests; Blood Volume; Cardiopulmonary Bypass; Chondroitin Sulfates; Dermatan Sulfate; Dogs; Drug Evaluation, Preclinical; Fibrinolytic Agents; Glycosaminoglycans; Hematocrit; Hemorrhage; Heparin; Heparitin Sulfate; Leukocyte Count; Molecular Weight; Platelet Count; Postoperative Complications; Random Allocation