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At least 19 recordsLinked to original sources
PubMed1985

[Severe early-onset thrombopenia induced by non-fractionated heparin: therapeutic trial with low molecular weight heparin].

A case of severe thrombocytopenia (27 x 10(3)/mm3) of early onset during unfractionated heparin (Héparine sodique Rovi) treatment is reported in a 75 year-old man suffering from a deep vein thrombosis of the right calf. It was not associated with thromboembolic or haemorrhagic complications. A serum heparin-dependent aggregating factor was not detected. Substitution of low molecular weight heparin (Choay Laboratory, CY 222, PM 4 500, 25 000 U anti-Xa/ml) for unfractionated heparin resulted in a progressive normalisation of the platelet count and improvement of the venous thrombosis.

Aged↗
PubMed2003

DX-9065a inhibition of factor Xa and the prothrombinase complex: mechanism of inhibition and comparison with therapeutic heparins.

Factor Xa (fXa) is the key enzyme of the prothrombinase complex that generates thrombin hence it is a good target for antithrombotic therapy. Here, the anti-fXa and anti-prothrombinase activities of DX-9065a which is an active-site directed inhibitor of fXa, and therapeutic heparins which are dependent on antithrombin (AT) for their anticoagulant function, were studied in amidolytic and proteolytic activity assays. It was found that DX-9065a is a competitive inhibitor of the Spectrozyme FXa (SpFXa) cleavage by both fXa and prothrombinase with similar K(i) values of approximately 10-20 nM. However, DX-9065a acted as a non-competitive inhibitor of prothrombin activation by prothrombinase with a Ki of approximately 26 nM. On the other hand, therapeutic heparins were effective catalysts of both fXa and prothrombinase inhibition by AT in the presence of SpFXa, but were ineffective in the presence of prothrombin. Further studies revealed that Tyr(99), a residue in the extended S2-S4 binding pocket of fXa, plays a key role in determination of specificity of the DX-9065a interaction.

Anticoagulants↗
PubMed1986

[Control of the therapeutic heparin dosage in platelet rich citrate plasma after protamine neutralization].

A laboranalytical method for estimating the anticoagulative effect of therapeutic heparin doses based on coagulation physiology is presented. Corresponding to our expectation this method is overcome by the direct measuring heparin with chromogenic substrates. On the other hand there are some advantages against the often practically used prolongation of PTT. By neutralisation of the heparin influence with protamine sulphate it is possible to discriminate between the heparin effect and additional disturbances in consequence of deficit in a coagulation factor. An absence of the heparin effect should always lead to the use of an antithrombin III assay.

Blood Platelets↗
PubMed1986

[Treatment of deep venous thromboses with heparin. Therapeutic management and biological monitoring].

Heparin may be administered either prophylactically (to prevent postoperative thromboembolic complications) or therapeutically (when thrombosis has occurred) and the dosages are very different. In addition, low molecular weight heparins are now available, and usually reserved only for prevention of thrombosis. The biological monitoring of these different therapies has evolved, and in addition to the classical tests like the recalcified plasma clotting time or the APTT, it is now possible to use more specific tests like the amidolytic activity of anti-IIa or anti-Xa. None of the simple tests alone is satisfactory for the verification of the efficacy of the treatment on a formed thrombosis or for detecting patients at high risk of haemorrhage. At this present state of our knowledge, the association of two of the preceding tests is recommended as any discrepancy could lead to the detection of an associated, unrecognised abnormality such as a circulating anticoagulant factor or thrombocytopaenia. The monitoring of classical prophylactic treatment generally only requires a very limited monitoring.

Acute Disease↗
PubMed2000

Therapeutic heparin concentrations augment platelet reactivity: implications for the pharmacologic assessment of the glycoprotein IIb/IIIa antagonist abciximab.

BACKGROUND: This study evaluated the effect of heparin on the platelet reactivity and the pharmacodynamic profile of abciximab. METHODS AND RESULTS: Ex vivo studies were performed on patients undergoing elective percutaneous coronary intervention (n = 26) who were at moderate to high risk of ischemic complications. Patients received a 12,000-U bolus of heparin followed by a 0.25-mg/kg bolus of abciximab. Before abciximab treatment, platelet aggregation responses to a variety of stimuli were assessed immediately before and 10 minutes after the heparin bolus. Heparin increased platelet aggregation to 2 and 5 micromol/L adenosine diphosphate (ADP) and 5 microg/mL collagen by 36%, 25%, and 46%, respectively (P < or =.001), but did not influence platelet reactivity to thrombin receptor-activating peptide or 20 micromol/L ADP and had no appreciable effect on platelet surface glycoprotein (GP) IIb/IIIa receptor numbers. To assess the impact of heparin on the pharmacodynamic profile of abciximab, GP IIb/IIIa receptor blockade and platelet aggregation inhibition estimates obtained after abciximab administration were calculated relative to the basal levels observed both before and after the heparin bolus. At 2 and 24 hours after the abciximab bolus, GP IIb/IIIa receptor blockade measurements normalized to either the preheparin or postheparin baseline determinations were equivalent. For all ADP concentrations tested, the 2-hour post-abciximab bolus platelet aggregation inhibition estimates based on the preheparin and postheparin baseline values were comparable. However, for 2 and 5 micromol/L ADP, the 24-hour post-abciximab platelet aggregation inhibition measurements based on preheparin baseline values were significantly lower than postheparin baseline determinations (both P < or =.003). In vitro studies revealed that therapeutic heparin doses induced a concentration-dependent reduction in the extent of platelet inhibition produced by amounts of abciximab that elicit partial inhibition of platelet aggregation. However, at abciximab concentrations that achieved platelet aggregation blockade of >80%, the levels of inhibition of platelet aggregation in the presence and absence of heparin were equivalent. CONCLUSIONS: The cumulative ex vivo and in vitro data indicate that for certain stimuli, heparin alters the platelet inhibitory profile of abciximab at concentrations of the agent that yield partial suppression of platelet function.

Abciximab↗
PubMed1997

Treatment of experimental mesangioproliferative glomerulonephritis with non-anticoagulant heparin: therapeutic efficacy and safety.

Treatment with conventional heparin is effective in experimental mesangioproliferative glomerulonephritis. However, the long-term effects and safety of this therapy, in particular in the presence of mesangiolysis, have not been assessed. In addition, this therapy has been hampered by bleeding complications. In the present study, therefore, we investigated the long-term effects of a short course of non-anticoagulant (NA) heparin treatment in the anti-Thy 1.1 mesangioproliferative glomerulonephritis, in which early immune-mediated mesangiolysis subsequently leads to mesangial hyperproliferation. Rats received continuous ip NA-heparin or vehicle during the active mesangioproliferative phase (Days 2 to 9; early treatment) or during the early resolution phase (Days 10 to 17; late treatment). Whereas NA-heparin in the early treatment group did not affect the glomerular macrophage, lymphocyte, or platelet influx, it did lead to significantly decreased glomerular cellularity, mesangial cell proliferation, alpha-smooth muscle actin, desmin expression (ie, markers of activated mesangial cells), and matrix accumulation as well as to persistent mesangiolytic lesions including microaneurysms. Despite this latter finding, at Day 120, NA-heparin-treated rats of the early treatment group showed significantly better renal function and less proteinuria and glomerulosclerosis than vehicle-infused rats. In contrast, late therapy with NA-heparin neither accelerated resolution of the nephritis or otherwise affected the course of the disease. We conclude that transient NA-heparin therapy is effective in mesangioproliferative glomerulonephritis, both acutely and long term, when it is initiated during the active phase of the disease. Also, NA-heparin therapy is safe even in glomerular diseases accompanied by mesangiolysis.

Aneurysm↗
PubMed1992

Therapeutic heparin monitoring service in a small community hospital.

Upon the request of members of the medical staff, the Pharmacy and Therapeutics Committee at Tawas St. Joseph Hospital began monitoring patients receiving full-dose continuous intravenous heparin therapy. Problems were noted in the usage of activated partial thromboplastin times and the resultant changes in heparin therapy. The problems identified during this quality assurance activity were addressed by a heparin protocol developed by a clinical pharmacist. The protocol includes giving patients a heparin loading dose of 50-100 units/kg actual body weight, an initial infusion rate of 15-20 units/kg/hr, and drawing the first activated partial thromboplastin time 6 hours later. After the results of the activated partial thromboplastin times are known, the protocol provides for further patient management and changes in infusion rates, if needed. A review of the heparin protocol use at 6 months after initial implementation, and 6 months after minor changes in the protocol, showed that clinical pharmacists improved heparin therapy in the patients they treated. Pharmacists used larger initial continuous infusion rates, less activated partial thromboplastin times during treatment, and patients they managed reached therapeutic activated partial thromboplastin time ranges earlier than patients treated by physicians. When voluntarily prescribed by physicians, full-dose continuous intravenous heparin therapy initiated and monitored by clinical pharmacists improved the quality of patient's anticoagulation treatment during hospitalization.

Clinical Protocols↗
PubMed1991

[Massive pulmonary embolism disclosing thrombocytopenia induced by low molecular weight heparin. Therapeutic success of prostacyclin].

The authors report a case of massive pulmonary embolism revealing thrombocytopenia induced by a low molecular weight heparin (LMWH) initially proposed for the treatment of superficial phlebitis. The diagnosis was confirmed by in vitro aggregation tests and a fall in the platelet count when the LMWH was reintroduced. The outcome was clinically, angiographically and hematologically satisfactory in response to in situ treatment with prostaglandin, subsequently replaced by Vitamin K antagonists.

Fibrinogen↗
PubMed2004

Decreased concentration of antithrombin after preoperative therapeutic heparin does not cause heparin resistance during cardiopulmonary bypass.

OBJECTIVE: To determine if preoperative heparin therapy causes an increase in the incidence of intraoperative heparin resistance by reducing the concentration of antithrombin in plasma. DESIGN: Prospective laboratory investigation of clinical samples. SETTING: Public tertiary care hospital and public pathology service. PARTICIPANTS: Forty-six patients undergoing cardiac surgery involving cardiopulmonary bypass. INTERVENTIONS: Fourteen patients received preoperative heparin therapy (POHI group) and 32 patients were controls (CONT group). MEASUREMENTS AND MAIN RESULTS: The concentration of antithrombin, activated coagulation time (ACT), and clinical parameters were measured at intervals. More POHI patients had on-bypass heparin resistance than CONT (43% and 3%, respectively, p < 0.01). The POHI group had a lower concentration of antithrombin than the CONT group before (80.9% and 92.6%, respectively, p < 0.01) and while on cardiopulmonary bypass (51.6% and 57.5%, respectively, p = 0.04). Comparison of heparin-resistant and heparin-responsive POHI patients showed that the concentration of antithrombin did not differ before bypass (82.4% and 79.8%, respectively, p = 0.53) or during bypass (51.8% and 51.4%, respectively, p = 0.91). In fact, antithrombin concentrations were slightly higher in the heparin-resistant POHI patients (not significant). POHI patients received more heparin than CONT patients (medians 787 U/kg and 600 U/kg, respectively, p = 0.01) and were transfused with more fresh frozen plasma on bypass (p = 0.03). CONCLUSIONS: Preoperative heparin causes an increased incidence of heparin resistance and reduced antithrombin concentrations. However, heparin resistance was not causally related to reduced antithrombin because antithrombin concentrations were not different between heparin-resistant and heparin-responsive patients in the POHI group.

Anticoagulants↗