RESUMEN

A patient with hypothyroidism had ingested aspirin and bled profusely following dental extraction. The only abnormalities noted on coagulation survey were a prolonged aspirin bleeding time and reduced retention of platelets on glass beads. Based on this index case, an additional 12 hypothyroid patients, on no medications, were evaluated for a mild bleeding disorder, including studies with aspirin challenge. The results indicate that thrombin-induced platelet serotonin release, following aspirin ingestion, was subnormal in most hypothyroid patients. However, only hypothyroid individuals with TSH levels of greater than 60 microU/ml have an increased hemostatic sensitivity to aspirin, as measured by the bleeding time test. These findings did not appear to result from decreased synthesis of the factor VIII-von Willebrand factor complex. As this drug is commonly ingested, the effects of aspirin on bleeding may explain the easy bruising and menorrhagia that occur in hypothyroid individuals.

Asunto(s)

RESUMEN

Twenty-nine heterosexual patients with hemophilia were investigated with histories, physical examinations, laboratory evaluations of immune function, delayed hypersensitivity skin tests, and assays for antibody to human T-cell lymphotropic virus type III (HTLV-III). Sixteen patients were HTLV-III antibody positive and 13 were HTLV-III antibody negative. No patient had the acquired immune deficiency syndrome (AIDS). Patients who had antibody to HTLV-III had received significantly more units and lots of factor concentrates in the preceding 5 years than those who did not have antibody. HTLV-III antibody-positive patients had significantly fewer total T cells (Leu-1 positive) and significantly fewer helper T cells (Leu-3 positive) than HTLV-III negative patients. Antibody-positive patients also had increased amounts of IgG and decreased thymidine incorporation in response to concanavalin A in vitro. There were no differences in in vitro lymphocyte responses to phytohemagglutinin (PHA), pokeweed mitogen, Candida, tetanus, or purified protein derivative (PPD), no significant impairments of gamma interferon or interleukin-2 (IL-2) production, and no anergy. Ten patients with antibody to HTLV-III had immunologic studies repeated 1 year after the original evaluation. A significant increase was seen in suppressor (Leu-2-positive) T cells but not in total T-cell or helper T-cell numbers, helper/suppressor ratios, or T-cell functional assays. We conclude that the immune abnormalities in hemophiliacs are the result of contact with HTLV-III but that these abnormalities may remain stable over prolonged periods.

Asunto(s)

RESUMEN

Various coagulation abnormalities are associated with pregnancy. Several investigators have suggested that there may be a unique procoagulant associated with amniotic tissue and fluid. We identified a cysteine proteinase from malignant tissue, cancer procoagulant, and had reason to believe a similar proteinase may be present in amniotic tissue. Amniotic fluid and extracts of amnion-chorion were purified by immunoaffinity chromatography with an antibody that was developed to cancer procoagulant antigen. The purified amnion-chorion procoagulant initiated clotting in normal and factor VII-deficient citrated human plasma and directly activated pure human factor X in a two-stage clotting assay. It was inhibited by 1 mmol/L of iodoacetamide and 0.1 mmol/L of HgCl2, and the procoagulant activity was activated by 10 mmol/L of KCN; these are classic properties of cysteine proteinases. The pure amnion-chorion procoagulant had the same mol wt and immunologic determinants as cancer procoagulant from rabbit V2 carcinoma, as determined by crossed immunodiffusion, suggesting that the same or very similar proteins were associated with both tissues. Thus, this procoagulant may be derived from both undifferentiated and dedifferentiated cells.

Asunto(s)

RESUMEN

Blood from adult male Wistar rats clotted rapidly in glass or siliconized tubes; the clots retracted and did not lyse. The serum prothrombin, plasma prothrombin and activated partial thromboplastin times were shorter than those of normal humans. In contrast, the thrombin and reptilase times were longer than those of normal human plasma, due apparently to the presence of a low-grade thrombin inhibitor in rat plasma. Coagulation factors, X, VIIIR:vW and IX assayed lower in rat than human plasma, while factors VIII:C and anti-thrombin III were higher. Values for other coagulation factors (II, V, VII, XI, XII and Fletcher) fell within the human range. Platelets were small and numerous. They aggregated well with ADP but poorly or not at all with collagen, ristocetin, thrombin, epinephrine, arachidonic acid and pig or bovine plasmas. Leukocytes numbered 4-8 X 10(3) cells/mm3, a near human range and were predominantly lymphocytic. Erythrocytes were small (MCV = 56-60 fl) and numerous (5.5-6.4 X 10(6) cells/mm3).

Asunto(s)

RESUMEN

Platelet function was analyzed in two hypothyroid patients who were taking methyldopa. Results from these two patients are compared to those obtained in seven others with hypothyroidism on no medications. Bleeding times in the two drug patients were 33 and 26 minutes compared to normal values (4.0 to 8.0 minutes) in the other hypothyroid individuals. In addition, platelet aggregation responses to epinephrine, collagen, and ristocetin were abnormal in these two patients; these were normal in the others with hypothyroidism. Repeat studies were done in the first drug patient when she was euthyroid and still receiving methyldopa. Her bleeding time decreased to 11 minutes, platelet retention increased from 31% to 75%, and abnormal aggregation responses corrected to normal. Factor VIII coagulant activity, VIII antigenic activity, VIII ristocetin cofactor activity, and two-dimensional immunoelectrophoresis of VIII antigen were normal. These findings suggest that methyldopa can potentiate the mild platelet function defect seen in patients with hypothyroidism.

Asunto(s)

RESUMEN

Comparison of continuous versus intermittent (every 12 h bolus) infusion of a high-purity Factor VIII concentrate in 12 severe hemophilia A patients undergoing surgical procedures indicated that a higher (50 u/dl versus 35 u/dl) minimal plasma level was seen with the same amount of product when given continuously. A continuous VIII concentrate infusion of 2 u/kg/h produces a mean VIIIc level of about 50 u/dl or, alternatively, about 0.04 u/kg/h raises the VIIIc level by 1 u/dl (1%). None of the patients showed any abnormal bleeding. Higher plasma levels of VIIIc were noted by the two-stage VIIIc assay than by the one-stage VIIIc assay. Fibrinogen levels were normal or only slightly elevated, and the monomer test was consistently negative.

Asunto(s)

RESUMEN

Lyophilized factor VIII concentrates, because of their convenience, are the most commonly used products for providing antihemophilic factor to patients with hemophilia A. Heightened concerns about associated complications indicate that cryoprecipitate usage will increase in the immediate future. We present a protocol for making cryoprecipitate more usable by "prepooling" individual units of cryoprecipitate in an "open" system. Our experience indicates this approach is safe, effective and acceptable to patients, including those on home therapy programs.

Asunto(s)

RESUMEN

A patient with hemophilia A developed T-cell deficiency characterized by infection with several opportunistic pathogens. Immunologic investigation showed cutaneous anergy, lymphocyte unresponsiveness to mitogens and antigens, an abnormal ratio of T-helper and T-suppressor cells with absolute lymphopenia and elevated IgA. The clinical and immunologic characteristics of this patient fit the recently described syndrome of opportunistic infections or Kaposi's sarcoma in patients with acquired T-cell deficiency; however, this patient does not have any of the associated underlying risk factors such as homosexuality, intravenous drug or amyl nitrite use, or positive serologic tests for syphilis. We conclude that the patient's acquired T-cell deficiency can be explained by exposure to a virus or other transmissible agent during factor VIII transfusions.

Asunto(s)

RESUMEN

Ten patients with porcine heterograft valves who were not receiving anticoagulant agents were evaluated to determine the effect of the valve on red blood cell survival and on platelet activation and consumption as measured by (1) quantification of the coagulation mechanism, (2) platelet function studies, and (3) 51-chromium platelet survival time. There was no evidence of significant intravascular hemolysis as determined by the reticulocyte count, serum iron and iron binding capacity, serum bilirubin level, or lactic dehydrogenase activity. The coagulation profile and the platelet function studies were normal. No statistically significant difference was found in the platelet survival time in the 10 patients with porcine heterograft valves (half-life 3.2 +/- 0.8 days) and the 11 normal control subjects (half-life 3.6 +/- 0.6 days) (p greater than 0.2). The finding of a normal platelet survival time in patients with porcine heterograft valves is consistent with clinical experience indicating that this device is associated with a low incidence of systemic embolization, approximating 3% per year.

Asunto(s)

RESUMEN

A colony of hemophiliac dogs was developed as descendants of a single affected Pomeranian. Over a 13 year period, a total of 29 hemophiliac dogs survived to the age of 6 months or longer. Eleven were female and 18 were male. All five of the possible matings in a sex-linked recessive inheritance pattern were accomplished and the offspring fell into the expected sex and disease groups. Twenty-one dogs died from untreated hemorrhages which usually occurred in loose tissues or body cavities during the night. Clinically, there were no hemarthroses but 22 other hemorrhages responded promptly to treatment with dog cryoprecipitate. Coagulation studies showed that the hemophiliac dogs averaged about 0.23 U/ml equivalents of human F VIII:C while normal dogs averaged 8.0 U/ml equivalents of human. F's V, VII, II, X, IX, XI and XII were higher than human in both normal and hemophiliac dogs. Dog fibrinogen fell within the human range and Fletcher F was very low.

Asunto(s)

RESUMEN

Seventeen patients with a spectrum of immunologically-related disorders were studied before and immediately after plasma exchange (PE) for changes in coagulation factors, complement, immunoglobulins, and immune complex levels. Each PE replaced 50 per cent of the plasma volume with 5% albumin and saline. With PE, coagulation profiles indicated a decrease of 23 to 55 per cent in the levels of fibrinogen, Factors II, V, VII, VIII, IX, X, XI, XII, and Fletcher factor. Only minimal changes were noted in the prothrombin time and activated partial thromboplastin time. Most coagulation factors, except fibrinogen, returned to baseline by 48 hours. Following three PE/week, fibrinogen was reduced by 51 per cent; other factors were not significantly altered. C3 and C4 fell by 35 to 40 per cent with each PE; these approached baseline by 24 hours. Immunoglobulins (G,A,M) were reduced by 34 +/- 3,37 +/- 3 and 34 +/- 3 per cent, respectively. After three PE, the total immunoglobulins were decreased by 50 to 55 per cent. Five of eight patients who had three or more PE developed hypogammaglobulinemia (IgG less than 450 mg/dl). Immune complexes were reduced by 50 +/- 4 per cent with each PE. Multiple exchanges in five patients led to a greater reduction (80 +/- 6%). Thus PE was an effective means of reducing immune complexes but led to hypogammaglobulinemia and hypofibrinogenemia.

Asunto(s)

RESUMEN

Coagulation profiles were performed in 30 consecutive alcoholic cirrhotic patients without known infection, malignancy, recent surgery, transfusion, or alcoholic intake. Hemorrhagic phenomena were present in 70% and included gastrointestinal bleeding, oozing from venipuncture sites, bruising, and epistaxis. All 30 patients had multiple liver function and coagulation abnormalities, the most frequent of which were increases in F VIII components and decreases in F XI and F VII. Also decreased in half or more of the 30 patients were Fletcher F, F II, F X, prothrombin time (PT), partial thromboplastin time (APTT), thrombin time (TT), reptilase time (RT), anti-thrombin III, and plasminogen. When comparing cirrhotic bleeders with nonbleeders, four parameters were significantly different in those with a bleeding tendency: F VII, anti-thrombin III, plasminogen, and albumin. The prolonged APTT was associated in four cases with a blocking inhibitor of unknown etiology. The prolonged TT and RT, in the absence of fibrin split products, fibrin monomers, DIC, or shortened euglobulin lysis time in any patient were suggestive of an abnormal fibrinogen, a dysfibrinogen. In three other patients, there was an inhibitor of the TT. Further investigation of the suspected dysfibrinogen in 21 patients by SDS-polyacrylamide gel electrophoresis revealed that the molecular weights of the Aalpha, Bbeta, and gamma polypeptide chains of fibrinogen were not different from normal. Two-dimensional immunoelectrophoresis of the suspected dysfibrinogen was similar to normal in 18 of 21 patients, with loss of the initial shoulder in three.

Asunto(s)

RESUMEN

The appearance of an acquired inhibitor to factor VIII clotting activity (F VIII:C) in a non-haemophiliac is an uncommon phenomenon; but, when it occurs, represents a difficult therapeutic problem. Cyclophosphamide has been the most frequently used form of therapy while corticosteroids, when used alone, have been felt to be ineffective. During the past 25 years, 18 of these patients have been evaluated in Pittsburgh. Their mean age was 63.7 years. Nine were female and nine male. Sixteen of the 18 received corticosteroids as their primary form of therapy. Eleven of the 16 (69%) showed clinical and laboratory improvement. Seven of the 11 had a complete response and the remaining four a partial response. Five patients demonstrated no improvement with corticoid therapy. The time to response varied from 4 to 41 d (mean 15.8). It was concluded that corticosteroids when used alone provide therapeutic results comparable to immunosuppressive therapy in the treatment of acquired inhibitors to F VIII:C and therefore represent a therapeutic alternative to immunosuppressive agents.

Asunto(s)

RESUMEN

The hypothalamic-pituitary-gonadal axis was evaluated in two groups of age-matched men with documented biochemical and histologic liver disease and compared to that of age-matched normal controls. Basal testosterone levels (p less than 0.05), spermatozoa concentrations (p less than 0.01), and seminal plasma volume (p less than 0.01) were reduced in the alcoholics studied with liver disease, but not the hemophiliacs with liver disease when compared to the normal controls. No difference in estradiol levels was noted between groups. Basal follicle-stimulating hormone and luteinizing hormone (LH) concentrations were increased (both p less than 0.01) in the alcoholics while only LH concentrations were increased (p less than 0.01) in the hemophiliacs compared to the normal controls. Gonadotropins (follicle-stimulating hormone and LH) and testosterone responses to clomiphene and to luteinizing hormone-releasing factor (LH only) in the alcoholic population studied, further distinguished the alcoholics from the hemophiliacs and the normal controls. The basal levels of the other anterior pituitary hormones (growth hormone and thyroid-stimulating hormone) as well as their provocative responses to thyrotropin-releasing hormone also distinguished the alcoholics from the hemophiliac population. Based upon these results, we propose that factors other than the liver disease per se are responsible for the disturbances of hypothalamic-pituitary-gonadal function observed in men with biochemically as well as histologically advanced stable liver disease.

Asunto(s)

RESUMEN

This report describes three patients with factor (F) VII deficiency: two adult siblings and an unrelated 5 1/2-month-old child who succumbed after several central nervous system (CNS) hemorrhages. This event prompted a review of the literature concerning the incidence and characteristics of intracranial hemorrhage in congenital F VII deficiency. Of 138 patients reported to have F VII deficiency, only 75 were considered to have a true deficiency. There was a 1:1 sex distribution with a 19% incidence of consanguinity in the 63 families which these 75 patients represented. CNS hemorrhage occurred in 12 of the 75 proven factor-deficient patients -- an incidence of 16.0%. There was a 1.4:1 female predominance in this group with a 44.4% incidence of consanguinity in their nine families. Except for one patient with hypertension, there was no history of preceding trauma or previous underlying CNS abnormality, though head trauma with a difficult vaginal delivery may have occurred in five infants. Diagnostic lumbar puncture or ventricular tap revealed bloody, xanthochromic cerebrospinal fluid in five. Five patients with F VII deficiency developed a CNS hemorrhage prior to 1 week of age, and none survived. Seven patients older than 1 week of age suffered such an event, and four of these survived. It is concluded that the greatest risk factor for development of CNS hemorrhage is trauma related to the birth process.

Asunto(s)

RESUMEN

The safety and usefulness of ibuprofen (Motrin) were evaluated in 15 patients suffering from hemophilic arthropathy via a double-blind protocol with individual crossover. No significant increase in hemorrhagic episodes or alteration in platelet function was observed. A decrease in morning stiffness was noted in nine patients, and three decreased markedly their use of other pain medications. We conclude that ibuprofen represents a relatively safe agent for the management of discomfort caused by hemophilic arthropathy in a select group of hemophilic patients.

Asunto(s)

RESUMEN

Transaminase values [alanine amino transferase (ALT) and aspartate amino transferase (AST)] and markers for hepatitis B were serially determined in 558 hemophiliacs exposed to blood products. Hepatitis B surface antigen (HBsAg) persistent for over 12 months was present in 6% of the patients. Antibody to hepatitis B surface antigen (anti-HBs) was noted in 90% of the 259 patients treated with factor VIII or IX concentrates but in only 49% of the 43 patients treated with fresh frozen plasma (FFP) or cryoprecipitate. Persistently abnormal transaminase values were noted in 31% of the patients treated with commercial concentrates but in only one (2%) of the patients exposed to cryoprecipitate or FFP. This difference continued even when the two groups of patients were matched for the amount of blood products, up to 50,000 units, which they had received in the study period. In the concentrate-treated patients, no correlation could be found between transaminase values and the number of units of factor VIII or IX they had received during the six years of the study (1973-1978).

Asunto(s)

Asunto(s)

Asunto(s)

RESUMEN

An analysis was made of 346 cases of disseminated intravascular coagulation (DIC) diagnosed by utilizing a combination of laboratory tests which reflect the pathophysiology of the syndrome. The goals of the study were three fold: 1) to compare our clinical disease categories with those of other investigators, 2) to re-evaluate the diagnostic tests and, 3) most importantly, to report the results of tests infrequently performed when evaluating DIC. The patients fell into the following groups: 1) infection -- 26%, 2) malignancy -- 24%, 3) surgery and trauma -- 19%, 4) liver disease -- 8%, 5) miscellaneous -- 23%. Of the diagnostic tests, those for fibrin split products (FSP), fibrin monomer and antithrombin III were the most valuable. Of the clotting proteins, factors II, V, VII and X were the most frequently decreased. The factor VIII: C levels were in conflict with the prevailing dogma. Factor VIII:C levels were decreased in only 9% of patients studied and, in fact, were increased in the majority of cases. Factor VIIIR:Ag and F VIIIR:vW were elevated in 80% of the patients evaluated. An overall mortality of 68% further confirms the dismal prognosis previously associated with DIC.

Asunto(s)