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Biomedical subjects

C S Kitchens

Publications and source records attributed to C S Kitchens.

At least 19 recordsLinked to original sources

Evolution of our understanding of the pathophysiology of primary mesenteric venous thrombosis.

Mesenteric venous thrombosis is a rare insidious event that is difficult to diagnose. Approximately half the cases in the past were deemed "primary" or "idiopathic." These cases were also frequently associated with a previous history of thromboembolism and a family history positive for thromboembolism. Inherited hypercoagulable disorders, such as deficiency of protein C, protein S, or antithrombin III, will probably explain many "primary" cases. Prompt diagnosis, especially with modern imaging techniques, and prompt anticoagulant therapy decrease mortality.

Humans

Changes in coagulation and anticoagulation in women taking low-dose triphasic oral contraceptives: a controlled comparative 12-month clinical trial.

OBJECTIVE: The effects of two triphasic oral contraceptives on coagulation and anticoagulation factors were compared in a 12-month open-label study. STUDY DESIGN: Fifty-two women (mean age 26 years) were enrolled in and completed the study; 20 had been randomly assigned to receive levonorgestrel plus ethinyl estradiol, 24 had been randomly assigned to receive norethindrone plus ethinyl estradiol, and eight surgically sterile women acted as untreated controls. Coagulation and anticoagulation factors were measured at baseline and during the sixth and twelfth months. RESULTS: Both oral contraceptives produced significant decreases from baseline in prothrombin time and partial thromboplastin time; there were also significant changes in laboratory control times. Factor XII was significantly increased in both oral contraceptive groups after 6 and 12 months. Fibrinogen antigen was significantly increased for norethindrone plus ethinyl estradiol after 6 and 12 months and for levonorgestrel plus ethinyl estradiol after 12 months. Platelet counts were unchanged. There was a significant increase in antithrombin III activity with norethindrone plus ethinyl estradiol at 12 months. Antithrombin III antigen was unchanged with the oral contraceptives; however, significant increases existed for alpha 1-antitrypsin antigen and plasminogen antigen and activity after 6 and 12 months and for alpha 2-macroglobulin antigen after 12 months for both oral contraceptives. alpha 2-Antiplasmin antigen was significantly increased for norethindrone plus ethinyl estradiol at the 12-month evaluation. There were no significant differences between the oral contraceptives for any coagulation or anticoagulation factor, and mean values generally remained within reference ranges. CONCLUSIONS: Levonorgestrel plus ethinyl estradiol and norethindrone plus ethinyl estradiol had equivalent, minimal effects on hemostasis, and changes in coagulation factors appeared to be balanced by changes in anticoagulation factors.

Adult

Hemostatic aspects of envenomation by North American snakes.

1. North American poisonous snakes have a wide spectrum of complex venoms. 2. Venom, especially that of the rattlesnakes, may cause a variety of hemostatic abnormalities by directly, yet only partially, cleaving fibrinogen, activating the fibrinolytic system, or activating and clearing platelets through the action of proteolytic enzymes. 3. Because these venoms do not result in the generation of thrombin, the syndrome is distinct from true DIC. Bleeding or thrombosis is rare. 4. As thrombin generation remains intact, hemostasis is largely preserved despite dramatic changes in hemostatic tests. 5. Therapy with heparin, blood, or blood products is rarely indicated. 6. Therapy with antivenin in selected cases is logical and efficacious.

Animals

Approach to the bleeding patient.

A broad, open, inquisitive, and semiskeptical mind must be used when approaching the bleeding patient. As in most endeavors in medicine, the history and physical examination provide an important baseline. Key laboratory tests must be quickly ordered and interpreted. Using this data base, one can quickly determine whether the hemorrhagic disorder is congenital or acquired, severe or mild, and progressive or stable. Hemostasis may fail owing to deficiencies of platelets, the plasma coagulation protein system, or endothelial disturbances. A precise diagnosis and appreciation of the tempo of the disorder will guide specific therapy.

Blood Coagulation Factors

Small bowel hematoma in a hemophiliac as a cause of pseudoappendicitis: diagnosis by CT imaging.

Acute abdominal pain in a hemophiliac should be approached as hemorrhage until proven otherwise. With factor replacement available, a conservative approach can be taken as opposed to immediate exploratory surgery. Diagnostic imaging can define areas of hemorrhage. We report a case of "pseudoappendicitis" in a hemophiliac with terminal ileum circumferential bowel wall hematoma diagnosed by CT with the initial diagnostic scan. Factor replacement resulted in resolution of the signs and symptoms of the pseudoappendicitis and follow-up CT scan revealed resolution of the hematoma. A review of the literature reveals few CT documented circumferential bowel wall hematomas with limited clinical histories and no cases with follow-up scans after conservative management.

Abdominal Pain

Factor XI: a review of its biochemistry and deficiency.

The biochemistry and physiology of Factor XI have been reviewed. The clinical history of our 25 patients was reviewed and compared with others' experiences. Factor XI deficiency remains enigmatic in that there is no correlation between Factor XI levels and clinical manifestations. Approximately 40 to 50% of all persons lacking Factor XI are of Ashkenazi Jewish extraction, and the remainder are represented by nearly all populations. Persons may be found to lack Factor XI because of evaluation for hemorrhage, evaluation of a prolonged PTT, or through family or other genetic studies. Hemorrhage is not as severe as in patients with hemophilia A or B. Data are presented suggesting that hemorrhage may, in part, be associated with aspirin use.

Adolescent

Prolonged activated partial thromboplastin time of unknown etiology: a prospective study of 100 consecutive cases referred for consultation.

The activated partial thromboplastin time (aPTT) is frequently used to assess overall competency of the intrinsic pathway of coagulation. An abnormal value may be caused by any of several abnormalities along this pathway or by many other variables including the presence of inhibitors, poor collection of the sample, or variables in the laboratory. When the cause for the prolongation is unknown to the requesting physician, the hematologist may be consulted. In this prospective study, the cause and perceived hemostatic risk to 100 consecutive patients referred to use for consultation regarding a prolonged aPTT of previous unknown cause were evaluated. We found that these abnormal aPTTs may be either indicative of a hemostatic defect, in 50% of the cases, or of no particular risk, in 36% of the cases. In 14%, the aPTT was artifactually prolonged. Most (81%) patients with a prolonged aPTT due to a hemostatic defect had an abnormal hemostatic history but some (19%) did not. Even among true abnormal tests, the degree of abnormality indicated little or nothing about hemostatic competency. We conclude that the cause of an abnormal aPTT is more important than the result itself. These data may be of use to those who consult on such matters.

Adult

Acquired hemophilia. A natural history study of 16 patients with factor VIII inhibitors receiving little or no therapy.

Rarely, a patient develops an antibody against factor VIII coagulant activity. The resultant hemorrhagic diathesis is clinically distinct from inherited hemophilia, being characterized by few hemarthroses but frequent skin and other soft-tissue hematomas. Hematuria may be troublesome. These patients represent therapeutic challenges. This study is one institution's results with 16 such patients followed up over an average of 31 months (range, four to 120 months; median, 19 months). It describes the largest group from a single institution receiving essentially no immunosuppressive agents, yet has one of the better overall results. Two patients experienced fatal hemorrhage and five patients underwent spontaneous remission. Long-term survival is not incompatible with persistence of the inhibitor. We conclude that this hemorrhagic diathesis is clinically distinct, less fatal than usually perceived, and may undergo spontaneous remission. Clearly, there is no mandate for any particular therapeutic regimen, such as immunosuppression, in the attempt to rid the patient of the antibody.

Adult

Clinical efficacy of desmopressin acetate for hemostatic control in patients with primary platelet disorders undergoing surgery.

Desmopressin acetate (DDAVP) is efficacious in patients with von Willebrand's disease. It additionally appears to have value in patients with uremic or aspirin-induced platelet dysfunction. We report here three patients with primary platelet defects who had previously experienced grossly inadequate hemostasis to whom we administered DDAVP. Each successfully underwent surgical procedures with DDAVP as the only hemostatic agent. Although the mechanism of these salutary effects is unclear, DDAVP may exert an influence directly on the endothelium independent of correcting abnormalities of the factor VIII:von Willebrand complex associated with von Willebrand's disease.

Adolescent

Physiology of hemostasis and its relationship to cardiovascular disease.

Our original understanding of coagulation was too simple. The waterfall or cascade system made sense but never gave clues either to points for control of the reaction or to areas to inhibit or reverse clotting. We now know critical points for control and reversal of hemostasis. By understanding more modern physiology, one is better able to design rational treatment programs to negate unwanted thrombosis. This chapter gives the reader a physiologic foundation to underscore the subsequent chapters.

Blood Coagulation

Anaplastic neoplasm in a patient with hairy cell leukemia.

A 63-year-old white man had a history of recurrent pneumonia, pancytopenia, and splenomegaly when the diagnosis of hairy cell leukemia was made on bone marrow biopsy examination. Splenectomy confirmed that diagnosis and his pancytopenia moderately improved. Three years following the diagnosis, the patient developed an upper abdominal mass involving the stomach wall that was found to be an anaplastic "large cell" neoplasm. Palliative radiotherapy was started, but the patient died 2 months later. Cytochemical studies of the anaplastic gastric neoplasm revealed cytoplasmic tartrate resistant acid phosphatase activity. Electron microscopy showed no epithelial differentiation. These observations suggest that the gastric neoplasm represented an evolution of hairy cell leukemia into a more aggressive tumor analogous to the transformation that occurs in other B-cell neoplasms.

Bone Marrow

Intensive short-term chemotherapy for patients with acute myelogenous leukemia: long-term follow-up.

Our pilot study addresses the problem of early relapse from complete remission in young adults with acute myelogenous leukemia (AML). Twelve patients with AML, 16-58 years of age, were entered in a study of four intense courses of cytotoxic chemotherapy using the following drugs: cytarabine, daunorubicin, 5-azacitidine, and 6-thioguanine. They received no maintenance therapy. Nine of 12 patients achieved complete response. With a minimum follow-up of 35 months, the observed disease-free survival at 2 years was 67% (14 +/- SE) and the actuarial disease-free survival at 4 years was 38% (17 +/- SE). It appears that brief intensive chemotherapy early in the management of AML can produce prolonged remission without the need for maintenance therapy.

Actuarial Analysis

A comparison between two commercially available activators for determining the partial thromboplastin time.

Activators that are used to determine the activated partial thromboplastin time should be sensitive enough to detect mild deficiencies of coagulation factors in a reproducible fashion. We compared two commercially available activators--a newly modified preparation of ellagic acid activator and a silica activator. Both reagents produced results that were reproducible over a broad range of concentrations of factors involved in the intrinsic coagulation pathway. The ellagic acid activator was more sensitive in detecting a partial deficiency of nearly all of these factors.

Adult

Factor XIII.

1. Activated factor XIII is the enzyme that covalently cross-links fibrin monomers into fibrin polymers and results in increased clot strength and resistance of the clot to fibrinolysis. 2. Small amounts (greater than 1% of normal) of factor XIII are necessary for normal in vitro and in vivo activity. 3. Factor XIII deficiency is a rare autosomal recessive illness in which a hemorrhagic diathesis is caused by the virtual absence of the active a subunit of factor XIII. Approximately 100 cases have been described. 4. The disease in homozygotes is characterized by umbilical stump bleeding, a high incidence of fetal wastage, delayed soft tissue hemorrhage, and a high incidence of intracranial bleeding. The heterozygote is asymptomatic. 5. This paper calls attention to the apparent high incidence of oligospermia and small testes seen in homozygote males. Otherwise secondary sex characterics are normal. 6. Because there is no abnormality in thrombin generation and conversion of fibrinogen to fibrin, route coagulation tests (prothrombin time, partial thromboplastin time, thrombin time, etc.) are normal. Platelet function tests are normal. 7. Clots made from recalcified plasma severely deficient in factor XIII are soluble in 5 M urea or 1% monochloroacetic acid. These screening tests are simple and nearly pathognomonic of the illness. 8. More sophisticated and quantitative tests (e.g., dansylcadaverine incorporation) are available for definitive diagnosis and heterozygote detection. 9. Replacement treatment of the illness is simple, effective, and relatively inexpensive. Due to the long half-life of infused factor XIII and the small amounts necessary for normal hemostasis, prophylaxis is feasible and encouraged.

Adult

Clinical observations of human bone marrow macrophages.

Although human bone marrow is usually obtained to examine precursors of formed elements of blood, important diagnostic information can be gleaned from study of macrophages. These cells are usually unnoticed. Macrophages may be involved in a number of different pathophysiologic mechanisms which are pointed out in this clinical and pictorial study. Inherited enzymatic deficiencies usually result in "storage cells" as exemplified by Gaucher disease. Relative deficiencies may be acquired if phagocytic activity overcomes normal enzymatic mechanisms.

Adult