Antithrombin III And Anti-Factor Xa Levels In Two Patients With Acute Promyelocytic Leukemia And Diffuse Intravascular Coagulation Treated With Heparin

1981 ◽  
Author(s):  
R M Sandler ◽  
H Liebman ◽  
M J Patch ◽  
A Teitelbaum ◽  
A Levine ◽  
...  

Serial blood coagulation studies in two patients with acute promyelocytic leukemia (APL) showed them to have disseminated intravascular coagulation (DIC) as evidenced by hypofibrinogenemia, positive plasma protamine sulfate paracoagulation tests and elevated fibrin degradation products. Serial samples were assayed for functional antithrombin- II I (AT-III) and anti-factor Xa (anti-Xa) activity before, during, and after heparin therapy. Heparin was detected by a modified thrombin time. AT-III was determined by fluorometric measurement of residual thrombin activity on a synthetic substrate (“Protopath” System, Dade Corporation, Florida, U.S.A.). Anti-Xa was determined by coagulation assay of residual Xa after prolonged incubation of prepared Xa with the test plasma. Patient #1 showed normal AT-III levels before and during heparin therapy, which fell to lower levels after the heparin was stopped. Anti-Xa was normal initially and then rose to very high levels during heparin therapy. There was an abrupt fall on cessation of heparin. Patient #2 showed normal AT-III levels at all times, but anti-Xa levels were initially low, rising to normal or high levels only when heparin was detectable in the plasma. It is concluded that neither DIC nor heparin necessarily cause a low AT-III activity in APL, and that therapeutic AT-III replacement may not be necessary. The anti-coagulant effect of heparin, as evidenced by a rise in the anti-Xa level, appears to be normal.

1981 ◽  
Author(s):  
R L Bick

Disseminated intravascular coagulation (DIC) is a frequent clinical entity spanning from a moderately severe bleeding disorder to a catastrophic, fulminant, and often fatal form usually associated with hemorrhage or, less commonly,as diffuse thromboses. The clinical and laboratory features of DIC remain confusing and controversial. To critically evaluate the usefulness of coagulation tests in aiding in the diagnosis and monitoring of therapy in DIC the clinical and laboratory findings were summarized in 48 patients with DIC. All patients were subjected to a prothrombin time (PT), activated partial thromboplastin time (PTT), reptilase time (RT), thrombin time (TT), fibrin(ogen) degradation products (FDP), platelet count, protamine sulfate test (PSO4), fibrinogen determination, and biological antithrombin-III (AT-III) level at the time of diagnosis. In addition, these same laboratory modalities were used to monitor patients during and after therapy. In this series of 48 patients, 38 patients had acute DIC and 10 patients had chronic DIC. In those patients with acute DIC, 100% of patients presented with hemorrhage and 53% of patients had thrombosis; 26% of patients died of their DIC type syndrome. In those patients with chronic DIC, 100% presented with hemorrhage, 80% presented with thrombosis, and none died of their intravascular clotting process. The probability of a pre-treatment abnormality in acute DIC was: FDP > AT-III = platelet count PS04 > TT > PT > fibrinogen level > PTT > RT. The probability of pre-treatment abnormalties in chronic DIC was: FDP > PSO4 = PT > AT-III = RT platelet count fibrinogen level = TT. These studies suggest the FDP level, the AT-III level, PSO4, and fibrinogen level to be reliable for aiding in the diagnosis of acute DIC. In chronic DIC the fibrinogen level, PS04, PTT, and AT-III level appear to be the most reliable indicies.


1977 ◽  
Author(s):  
R.L. Bick ◽  
M.L. Dukes ◽  
W.L. Wilson ◽  
L.F. Fekete

Antithrombin-III (AT-III )/heparin cofactor is now recognized as a major inhibitor of thrombin and other serine proteases in coagulation. Since the reaction between AT-III and serine proteases is irreversable.AT-III consumption should be expected in pathological intravascular coagulation and attendent generation of thrombin and other serine proteases. Using a new AT-III assay system, unaffected by heparin or fibrino(geno)lytic degradation products, AT-III was monitored in 17 patients with DIC, It was found that early and significant decreases occured in all pts. It was further noted that monitoring of AT-III during therapy for DIC reflected a cessation of AT-III consumption and, thus, appeared to reflect efficacy of therapy in stopping the clotting process. Only 1 of 17 patients failed to show an increase in AT-III with initiation of therapy. In this group of patients, mini-heparin therapy appeared to be as efficacious as large doses of heparin in correcting AT-III consumption and other laboratory abnormalities of acute DIC, and in controlling hemorrhage of acute DIC. Four patients had chronic DIC with malignancy; the use of ASA and dipyridamole corrected AT-III consumption and clinical manifestations in these patients, although the response required more time than with heparin or mini-heparin. These findings suggest that the monitoring of DIC with AT-III levels may be useful in both confirming the diagnosis and, more importantly, in monitoring efficacy of therapy. Significant rises in AT-III were noted in all but 1 patient after initiating therapy, presumably reflecting cessation of consumption. In addition, mini-heparin appeared to be as efficacious as large heparin doses in stopping acute DIC and antiplatelet therapy appeared to stop AT-III consumption and clinical manifestations in patients with chronic DIC associated with malignancy.


1981 ◽  
Author(s):  
K Zawilska ◽  
M Kanamicki ◽  
P Psuja ◽  
J Sowier ◽  
S Kawczynski ◽  
...  

In a series of 21 patients with serious Gram-negative and Gram-positive infections, 5000u. heparin was admini- stred subcutaneously 12-hourly with the aim of reducing the incidence of disseminated intravascular coagulation.Before starting heparin therapy there were prolongation of partial thromboplastin time; moderately increased levels of fibrinogen degradation products (FDP); decreased antithranbin III (AT III) activity (measured with chromogenic substrates); and positive paracoagulaticn tests.On heparin therapy FDP decreased and platelet count and AT III increased; and there were no clinical or laboratory signs of DIC. In those who died there were no postmortem signs of intravascular fibrin deposition.19 of the 21 patients developed septic shock. These received standard therapy as well as subcutaneous heparin. 14 patients (66%) died. There were no complicaticns with heparin therapy.In serious infections prophylactic subcutaneous heparin is advisable as early as possible.


1973 ◽  
Vol 30 (03) ◽  
pp. 471-479 ◽  
Author(s):  
K. W. E Denson ◽  
John Bonnar

SummaryA method for the measurement of heparin utilising the potentiating effect of heparin on the action of anti-factor Xa is described. The effect on the assay of platelet contamination of plasma, the presence of fibrinogen degradation products and low levels of anti-factor Xa have been studied. The assay method has been compared with the calcium thrombin time method and a group of obstetrical patients have been studied using both methods.


Blood ◽  
1973 ◽  
Vol 41 (4) ◽  
pp. 489-496 ◽  
Author(s):  
Jean Bernard ◽  
Marise Weil ◽  
Michel Boiron ◽  
Claude Jacquillat ◽  
Georges Flandrin ◽  
...  

Abstract Daunorubicin induces complete remissions in about 50% of patients with acute promyelocytic leukemia. The median duration of these remission is 26 mo. Failures are mainly due to hemorrhages as a result of disseminated intravascular coagulation during the first 5 days (25%) or due to sepsis during the second and third week (25%). Long-term survivals are more frequent than in the other acute granulocytic leukemias.


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