Clinical and Applied Thrombosis/Hemostasis

There is no consensus concerning thromboembolic prophylaxis in high-risk pregnant women with a previous his tory of heparin-induced thrombocytopenia. An alternative an ticoagulant therapy is danaparoïd, whereas unfractioned and low-molecular-weight heparin therapy is contraindicated. We report a case of successful thrombosis prophylaxis using dan aparoid in a high-thrombosis-risk pregnant woman with a his tory of heparin-induced thrombocytopenia during a previous pregnancy and Widal's disease.

Circulating anticoagulants are endogenously pro duced substances that interfere with in vitro tests of coagulation like activated partial thromboplastin time (APTT), and cause prolongation of the clotting times. Evaluation of the abnormal APTT involving various factor assays and mixing studies may provide inconclusive and ambiguous results. Tissue thrombo plastin inhibition test (TTIT) is one of the screening assays for detection of circulating anticoagulants. However, this test is influenced by the presence of unfractionated heparin (UFH) from concentrations 0.2 U/mL and higher. Since low- molecular-weight heparins (LMWHs) are increasingly used for the prevention of thrombotic disorders and may replace UFH in the future, in this study the authors studied the influence of LMWHs on the performance of TTIT and compared the results with UFH. UFH and LMWHs showed a prolongation of TTIT in the concentration range of 0.25-1.0 U/mL. The marked pro longation of the TTIT with UFH and different LMWHs is in decreasing order of UFH > ardeparin > tinzaparin > dalteparin > enoxaparin. Patients with circulating anticoagulants who are given LMWHs may have false-positive results of TTIT and this influence should be kept in mind during patient management.

The authors evaluated the hemostatic abnormalities occurring in the postoperative period of eight patients with malignant tumors and compared them with those occurring in the postoperative period of eight patients with benign tumors. Two of the patients with malignant tumor presented pulmonary embolism after operation. Plasma fibrinogen and fibrin degra dation product levels in patients with malignant tumors were already high before operation and further increased signifi cantly after operation. The plasma levels of D-dimer, thrombi n-antithrombin complex, and free-tissue factor pathway inhibi tor were increased in both groups after operation, but they were higher in patients with malignant tumors than in patients with benign tumors. The plasma levels of protein C and antithrom bin were significantly decreased in both groups after operation, but they were significantly lower in patients with malignant tumors than in those with benign tumors. The decreased activ ity of protein C or antithrombin may be not only a risk factor of thrombotic disease, such as pulmonary embolism, but also the cause of thrombosis. In patients with malignant tumors, the operation time was significantly longer than that in patients with benign tumors. This long operative period might cause vascular endothelial cell injury which is reflected by the plasma levels of free-tissue factor pathway inhibitor, antithrombin, and protein C.

Activation of the coagulation system in the alveo lar space plays an important role in the pathogenesis of inter stitial lung disease (ILD) and pulmonary fibrosis. The protein C (PC) pathway is the main modulator of coagulation activation. This study evaluated whether dysfunction of the PC pathway is associated with increased collagen synthesis in the intraalveolar space of patients with ILD. This study comprised 22 patients with ILD; of these, five had idiopathic pulmonary fibrosis (IPF), nine had sarcoidosis-associated ILD, and eight had col lagen vascular disease-associated ILD (CVD-ILD). Thrombin— antithrombin complex (TAT) was measured as a marker of coagulation activation. As markers of the PC pathway activity, the concentration of activated PC-PC inhibitor (APC-PCI) complex and the APC-PCI/PC ratio were measured and, as a marker of collagen synthesis, the concentration of aminotermi nal propeptide of type III procollagen (PIIINP) was measured in bronchoalveolar lavage fluid (BALF) of ILD patients. TAT was significantly increased in BALF from ILD patients as com pared to control subjects. The concentrations of PIIINP were significantly elevated in patients with ILD as compared to healthy subjects. In contrast, the concentration of APC-PCI and the values of APC-PCI/PC ratio were significantly de creased in BALF from patients with ILD. BALF concentration of PIIINP was significantly and inversely correlated with the concentration of APC-PCI and with the APC-PCI/PC ratio. These findings suggest that dysfunction of the protein C path way may have important physiopathologic implications in the development of pulmonary fibrosis in ILD.

Low-molecular-weight heparins (LMWH) are widely used as antithrombotic prophylactic pharmaceutical agents in orthopedic and general surgery. Their antithrombotic characteristics are expressed by plasma mediators such as anti- Xa, anti-IIa, and increased release of tissue factor pathway inhibitor (TFPI) from vascular endothelium. The purpose of this clinical research is to study the relation between plasma levels of these mediators and postoperative bleeding.

Forty-one consecutive patients undergoing hip or knee ar throplasty (n = 36) and colectomy (n = 5) received the stan dard enoxaparin (a LMWH) dose preoperatively (general sur gery) or immediately postoperatively (orthopedic surgery). Ma jor bleeding was defined as a postoperative drop of ≥ 5 g/dL) of hemoglobin. The authors observed that there was a linear relationship between an increase in free/total TFPI ratio levels and postoperative bleeding. When that ratio increased by >60%, the hemoglobin dropped to >5 g/dL (n = 17).

This relationship between free/total TFPI ratio increase and postoperative bleeding was statistically significant (P < 0.001). Those who did not bleed (hemoglobin drop was less than 5 g/dL) (n = 24) had a ratio increase (if any) of less than 50%. However, the authors did not observe any statistical relation ship between anti-Xa, anti-IIa, or prothrombin time and post operative bleeding in patients receiving LMWH for deep vein thrombosis prophylaxis in orthopedic and general surgery pa tients. The authors recommend a pre- and postoperative ratio level measurement whenever major bleeding is anticipated, as adjustments of LMWH dose or frequency might be necessary.

The levels of interleukin-6 and platelet-derived microparticles (PMPs) were measured in the blood of 137 pa tients with side effects from platelet concentrate (PC) transfu sion with leukocyte removal filtration, P-selectin-expressing platelet and PMPs in stored PC before and after the filtration, and filtered leukocytes positive for P-selectin glycoprotein li gand-1. The side effects, which were observed in 203 transfu sions for 84 patients with hematologic disease and 53 patients with nonhematologic disease with no significant difference be tween the two groups, included urticaria (75.9%), erythema (18.7%), and fever (17.2%), but no anaphylactic reactions. The levels of interleukin-6 and PMP correlated in both groups, and were significantly higher in the hematologic disease group than in the nonhematologic disease group. The level of PMP, but not interleukin-6, was significantly higher for patients testing posi tive for allergic reaction than for those testing negative. In the stored PC prior to filtration, the level of interleukin-6 was normal. The level of P-selectin-expressing platelets and PMPs was elevated before filtration, but was significantly lower after filtration. Taken together, the results suggest that PMP is in volved in the generation of transfusion reactions, and indicate that both platelets and PMP displaying P-selectin bind to P- selectin glycoprotein ligand-1 of leukocytes retained by the leukocyte filter.

Aspirin (ASA) does not effectively lower platelet aggregation in all people. The platelet aggregation (PA) score is an easily used clinical method for measuring the effect in individuals of antiplatelet medications. Fifteen apparently healthy subjects (2 men and 13 women), selected for their resistance to ASA's antiaggregation effect, completed a se quential trial of ticlopidine, Alka-Seltzer®, and ASA + citric acid (CTA). Ticlopidine was the strongest aggregation inhibitor and the ASA + CTA combination was more inhibitory than Alka-Seltzer. It was determined that measuring antiaggregation effects of a particular agent in an individual prior to usage would optimize treatment. The PA score methodology provides a means for testing patients prior to antiplatelet therapy for prevention and treatment of the thrombotic complications of vascular disease.

In order to provide sustained hemostasis or tissue sealing, fibrin sealants must generate adhesive clots with me chanical properties capable of resisting forces, such as shear, that might break or tear the clot. Commercial preparations of fibrin sealants should generate clots of adequate and consistent mechanical strength. The mechanical strength of fibrin sealants is often measured as bonding strength in in vivo or ex vivo animal wound models. These tests can be useful predictors of clinical efficacy. However, these, as well as many in vitro tensile strength tests for fibrin sealant, tend to be laboratory specific and require extensive reagent preparation time and analyst training. The thromboelastograph has historically been used to screen for plasma protein and platelet disorders that lead to defective clot formation. The authors have developed a simple in vitro test, using a standard thromboelastograph that can provide reliable, reproducible information on the rheology of clots generated by fibrin sealant preparations. Using this method, the shear strength of fibrin sealant clots was measured and shown to correlate with the fibrinogen, but not the throm bin, concentration in the sealant. Shear strength was also shown to correlate with the sealant concentration of the fibrin cross- linking proenzyme, factor XIII. Sealants containing lysine, which can act as an alternate substrate for factor XIII enzyme and prevent efficient fibrin chain cross-linking, were shown by this method to generate clots of substantially reduced shear strength. The method distinguished between thrombin- catalyzed clot formation and other fibrinogen clotting mecha nisms as evidenced by the significantly lower shear strength associated with batroxobin-generated fibrin clots.

Patients treated with L-asparaginase may present with hemorrhagic and thrombotic cerebrovascular events. This syndrome generally occurs after a few weeks of therapy and may occur after L-asparaginase therapy is completed. Compli cations appear to result from depletion of plasma proteins in volved in coagulation and fibrinolysis. Seizures are uncommon symptoms, and are always caused by cerebrovascular events. We report a case of seizure associated with L-asparaginase therapy but no evidence of hemorrhagic or thrombotic cerebro vascular events.