Cardiovascular surgery in patients with congenital plasma coagulopathies.

From 1978 to 1986, fifteen cardiovascular operations were performed on 13 patients with known congenital bleeding disorders. The patients (10 men and 3 women) had a mean age of 51.1 +/- 3.4 years. Four were seen with cardiovascular lesions and documented hemophilia A (Factor VIII deficiency); 3 had hemophilia B (Factor IX deficiency); 3 had Factor XI deficiency; 2 had von Willebrand's disease, and 1 had dysfibrinogenemia. All patients had a history of major hemorrhage after dental extractions or general surgical procedures, and had clearly documented coagulation disorders on hematological evaluation. Elective cardiovascular procedures performed in these patients included aortocoronary bypass grafting (eight), cardiac valve replacement or repair (five), aortic graft placement (one), and carotid endarterectomy (one). The mainstay of perioperative management included appropriate replacement therapy with blood components. Coagulation factor levels were measured routinely to guide therapy. There were no deaths. Two hemorrhagic complications necessitated reexploration. We conclude that in patients known to have congenital coagulation disorders, cardiovascular operations using systemic heparinization can be performed with minimal morbidity and mortality when carried out with preoperative and perioperative support from the hematology service, adequate replacement therapy using blood components, and careful monitoring of the coagulation status.

Characterization of a variant prothrombin in a patient congenitally deficient in factors II, VII, IX and X.

An 18-month-old child, who had no evidence of liver disease, malabsorption, or chronic ingestion of coumarin compounds, was found to have plasma deficiencies of factors II, VII, IX and X. Assays for factor II and X by immunological techniques (antibody neutralization and immunoelectrophoresis) revealed normal or elevated antigenic activity of these factors, suggesting the presence of abnormal protein variants in the patient's plasma. On two-dimensional immunoelectrophoresis of the patient's plasma in calcium, a normal and an abnormal population of prothrombin were seen. The abnormal prothrombin had a mobility more anodal than that of normal prothrombin, but less anodal than that of acarboxyprothrombin. The abnormal prothrombin, in contrast to acarboxyprothrombin, adsorbed readily to both aluminum hydroxide and barium citrate, and could be identified by two-dimensional immunoelectrophoresis of a barium citrate eluate. We suspect that the abnormal variant represents a partially carboxylated prothrombin.

Congenital deficiency of blood clotting factors II, VII, IX, and X.

A patient congenitally deficient in factors II, VII, IX, and X has been further investigated after a follow-up of 15 yr. At birth, these factors, when determined by clotting assays, were undetectable. Following therapy with vitamin K1, the clotting activity of these factors rose but never exceeded 18% of normal. Immunologic assays revealed much higher levels of these factors than did clotting assays, thus suggesting that the vitamin-K-dependent factors were present in abnormal forms. Two-dimensional crossed immunoelectrophoresis showed that at least two forms of prothrombin were present in the patient's plasma. One form was similar to normal prothrombin; the other had the same mobility as acarboxyprothrombin. In addition, the majority of this fast-migrating peak was not adsorbable onto insoluble barium salts. These observations suggested that some molecules of the patient's prothrombin lacked the normal complement of gamma-carboxyglutamic acid residues. This observation was confirmed by a specific assay for gamma-carboxyglutamate. Since malabsorption of vitamin K, warfarin intoxication, and hepatic dysfunction were excluded as causes of this patient's syndrome, this rare congenital abnormality could represent either a defective gamma-carboxylation mechanism within the hepatocyte or faulty vitamin K transport.

Surgery in patients with congenital disorders of blood coagulation.

Surgical procedures on patients with congenital disorders of blood coagulation can be performed with a high degree of confidence and an acceptable incidence of complications. During the period 1960-1975, 42 patients with congenital disorders of blood coagulation underwent 94 operative procedures at the New York Hopital-Cornell Medical Center. The coagulation defect was diagnosed preoperatively, in nearly all patients. Careful hematologic management, including specific factor replacement, is essential. The importance of meticulous hemostasis at surgery and careful monitoring of blood coagulation in the postoperative period is strongly emphasized.