Monette Jeter

Envenomation by the northern blacktail rattlesnake (Crotalus molossus molossus): report of two cases and the in vitro effects of the venom on fibrinolysis and platelet aggregation

In two cases of human envenomation by the northern blacktail rattlesnake (Crotalus molossus molossus) there was marked swelling and ecchymosis of the bitten extremity and thrombocytopenia and, in one case, hypofibrinogenemia. Treatment consisted of i.v. antivenin, crystalloid solution, fresh frozen plasma and cryoprecipitates, with recovery in each case. In vitro studies showed that the venom had fibrinolytic and platelet aggregating properties; a coagulant effect, although present, was much less marked.

Fibrinolysis after acute ischemic stroke.

Abstract Stroke is a thrombotic process in at least 80% of cases. The acute phase of stroke is characterized by brisk thrombin activity and relatively depressed fibrinolytic activity. The presence of inhibitors of plasminogen activation may play a role in this impairment of fibrinolytic activity. Fibrinolytic activity rises slowly in the subacute phase after a stroke, but the contribution of specific activators and inhibitors during this time has not been delineated. These findings have important implications for the treatment of acute stroke. An important question remains as to whether all these changes are secondary to the stroke, or whether preexisting abnormalities of fibrinolysis contribute to the occurrence of a stroke. Large prospective epidemiologic studies using current techniques are necessary to determine whether fibrinolytic abnormalities are risk factors for stroke. [68] If this is so it would provide an important means of identifying patients at high risk for stroke. Further, it might eventually lead to new strategies of stroke prevention via augmentation of the fibrinolytic system.

Danazol-induced factor VIII and IX by passing activity in hemophiliacs

Danazol, a synthetic androgen reported to increase factor VIII and IX activity levels, was given to 6 hemophiliacs. With danazol therapy (600 mg/da) the APTTs shortened by 30-45% of pre-treatment times. However, the activity levels of the deficient factors did not increase significantly nor consistently with the APTT change. The prothrombin times and activity levels of factors XI and XII also did not change during the study period. Addition of plasma from danazol-treated patients to plasma with a known factor VIII inhibitor and to plasma from an untreated severe hemophilia A patient caused a similar shortening of the respective APTTs. Absorption of the danazol plasma with precipitating antibody against factor VIII and IX did not remove the APTT correcting principal. The data suggest that danazol may cause the de novo appearance of an intrinsic coagulation pathway activator having factor VIII and IX bypassing activity.

Effects of chronic β‐carotene supplementation on vitamin K status in adults

Abstract Plasma vitamin K concentrations and prothrombin coagulation activity were determined in 26 normal adults who had received daily (S‐carotene supplementation (0,15,30, or 60 mg) for six months. Neither plasma vitamin K nor coagulation activity were significantly decreased at any supplementation level. Thus, chronic β‐carotene supplementation, even at high daily doses, is not expected to result in clinical vitamin K deficiency. The data suggest separate mechanisms for intestinal absorption of β‐carotene and vitamin K.

CORD BLOOD COAGULATION CHANGES IN MATERNAL HYPERTENSIGN

The occurrence of thrombocytopenia and disseminated intra-vascular coagulation (DIC) are newborn hematologic manifestations of maternal hypertension syndromes. Since hepatic disease occurs in mothers with preeclampsia-eclampsia we examined the levels of various coagulation factors to determine if other coagulopathies exist other than DIC. Fifty-three (53) cord blood samples were studied (PTT; pro time; fibrinogen, factors II, V, VII, VIII, IX, X, XII levels). There were 30 normal term controls, 6 with pregnancy-induced hypertension (PIH) and 17 with moderate to severe preeclampsia (PRE). Newborns with asphyxia were excluded. The mean gestational age was 37 in the two study groups; APGARs were 8/9 in PIH and 7/8 in PRE. The significant changes (*) are shown in the Table (mean ±SE).Reduced factor VII and V with elevated factor VIII levels in the PRE group suggest liver damage as the cause of the coagulopathy. Elevated factor VIII levels was the only abnormality found in PIH neonates. No infant had DIC or evidence of vitamin K deficiency. Hepatic dysfunction may be a major manifestation of infants born of toxemic mothers.

DANAZOL-INDUCED FACTOR IX AND VIII BYPASSING ACTIVITY

Danazol, a synthetic androgen reported to increase factor VIII and IX activity levels, was given to 5 hemophiliacs who were >17 years old (3 with severe hemophilia A, one moderate hemophilia A and one moderate hemophilia B). With danazol therapy (600 mg/da) the PTTs shortened 20-30% of pre-treatment times. The prothrombin times and activity levels of factors VIII, IX, and XII did not change during the study period. Addition of plasma from danazol-treated patients to plasma with a known factor VIII inhibitor and to plasma from an untreated severe hemophiliac A patient caused a similar shortening of the respective PTTs. A typical mixing experiment is shown in the Table (IP=inhibitor plasma; NP=normal plasma; HP=hemophilia A control; HP-D=danazol plasma in hemophilia A. The PTTs, in secs, are shown using 1 vol to 1 vol mixing, incubating for 4 min @ 37°C).Absorption of the danazol plasma with precipitating antibody against factor VIII and IX did not remove the PTT correcting principal. The data suggest that danazol may cause the de novo appearance of an intrinsic coagulation pathway activator having factor VIII and IX bypassing activity.

EFFECT OF DANAZOL ON APTT, COAGULANT FACTOR ACTIVITY AND BLEEDING IN HEMOPHILIA

Danazol has been reported to raise several plasma proteins. Danazol was given orally at 600 mg/day in 3 divided doses to 6 hemophiliacs for 8-14 weeks. Factor levels, APTT and other laboratory parameters were measured every 2 weeks. Five patients had classic hemophilia (1 mild-moderate, 3 severe, 1 with inhibitor) and 1 had Christmas disease. All patients showed a significant decrease an APTT beginning with the first measurement (2 weeks) and persisting till the drug was discontinued. However, a corresponding increase in the deficient factor activity could not be consistently demonstrated. Typical results for a severe classic hemophiliac are shown.Despite the shortened APTT bleeding episodes continued in the severe hemophiliacs and the patient with Christmas disease. In 4 patients bleeding appeared to either increase in severity or change in pattern. In 2 patients bleeding did not respond to their usual factor infusions, but responded to discontinuation of danazol and further factor replacement. In 3 patients the drug was discontinued because of bleeding. These results differ from those recently reported. Increased fibrinolytic activity may be responsible for the altered bleeding.