Search

Objective: Heterozygous Factor V R506Q [Factor V Leiden (FVL)] and prothrombin G20210A (PGM), the most common inherited thrombotic disorders in the Caucasian population, confer a low-moderate risk for first venous thromboembolic (VTE) event. We investigated the thrombotic complications of rare homozygous and compound heterozygous FVL and PGM., Methods: A cohort of patients with homozygous and compound heterozygous FVL and PGM were evaluated at a major referral center in Central Pennsylvania, USA between June 2001 and March 2019. Data including incidence of first and recurrent thrombosis, associated risk factors, family history and demographics were collected., Results: Seventy-five patients were eligible for analysis: 47 had homozygous FVL, three had homozygous PGM, 19 had compound heterozygous FVL and PGM, five had compound homozygous FVL and heterozygous PGM, and one had compound heterozygous FVL and homozygous PGM. Fifty-nine patients experienced 111 thromboembolic events. Forty-seven percent of first thrombotic events occurred in patients without clinical or surgical conditions predisposing to thrombosis. The rate of recurrent thromboembolism was 59%. The mean time to recurrence was 8.5 years. Ninety percent of recurrent events occurred during times when patients were not treated with anticoagulation., Conclusion: Persons with homozygous and compound heterozygous FVL and PGM are at a significantly increased risk of first unprovoked and recurrent VTE. Patients with first thromboembolic events should be considered for long-term anticoagulation., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Inherited Factor V deficiency is a rare bleeding disorder. We describe the genetic analysis and anesthetic management of a parturient with severe Factor V deficiency who presented in spontaneous labor. Good hemostatic conditions were obtained with prophylactic fresh frozen plasma administration of 10 mL/kg. Detailed genetic analysis by next-generation sequencing identified several relevant mutations in the coding part of the Factor V (F5) gene in our patient, her parents, and the newborn.

A 60-years old patient was admitted to a community hospital with septic arthritis. He was treated with antibiotics and subcutaneous unfractionated heparin (UH) was used for venous thromboprophylaxis. After three days, he developed leg deep venous thrombosis and was treated with IV heparin. One day later, the patient developed pulmonary emboli, which was found using ventilation/perfusion scan. He was transferred to the University Hospital for further management. Upon arrival, antibiotic and intravenous UH were continued. Trans-Esophageal Echocardiogram showed a thrombus in the right atrium, a small portion of which extended to the left atrium through a patent foramen ovale. Another large thrombus was noted in the right ventricle, which extended to the pulmonary artery. Review of the patient's medical records revealed a halving of his platelet count three days following the heparin administration. Therefore, HIT seemed very likely. Intravenous UH was stopped and an emergency thrombectomy was performed. ELISA testing of HIT antibodies came negative. This made HIT diagnosis unlikely and the patient received dalteparin. A week later, as the platelet count declined again, HIT antibodies' testing using ELISA and C-14 serotonin release was repeated, and both assays were positive. Argatroban was restarted and the platelet count normalized.

Immunoproliferative small intestinal disease (IPSID) was recently added to the growing list of infectious pathogen-associated human lymphomas. Molecular and immunohistochemical studies demonstrated an association with Campylobacter jejuni. IPSID is a variant of the B-cell lymphoma of mucosa-associated lymphoid tissue (MALT), which involves mainly the proximal small intestine resulting in malabsorption, diarrhea, and abdominal pain. Geographically, IPSID is most prevalent in the Middle East and Africa. IPSID lymphomas reveal excessive plasma cell differentiation and produce truncated alpha heavy chain proteins lacking the light chains as well as the first constant domain. The corresponding mRNA lacks the variable heavy chain (V(H)) and the constant heavy chain 1 (C(H)1) sequences and contains deletions as well as insertions of unknown origin. The encoding gene sequence reveals a deletion of V region and parts of C(H)1 domain. Cytogenetic studies demonstrated clonal rearrangements involving predominantly the heavy and light chain genes, including t(9;14) translocation involving the PAX5 gene. Early-stage IPSID responds to antibiotics (30%-70% complete remission). Most untreated IPSID patients progress to lymphoplasmacytic and immunoblastic lymphoma invading the intestinal wall and mesenteric lymph nodes, and may metastasize to a distant organ. IPSID lymphoma shares clinical, morphologic, and molecular features with MALT lymphoma, lymphoplasmacytic lymphoma, and plasma cell neoplasms.

Surfactant protein A (SP-A) plays a role in innate host defense. Human SP-A is encoded by two functional genes (SP-A1 and SP-A2), and several alleles have been characterized for each gene. We assessed the effect of in vitro expressed human SP-A genetic variants, on TNF-alpha and IL-8 production by THP-1 cells in the presence of bleomycin, either before or after ozone-induced oxidation of the variants. The oligomerization of SP-A variants was also examined. We found 1) cytokine levels induced by SP-A2 (1A, 1A(0)) were significantly higher than those by SP-A1 (6A(2), 6A(4)) in the presence of bleomycin. 2) In the presence of bleomycin, ozone-induced oxidation significantly decreased the ability of 1A and 1A/6A(4), but not of 6A(4), to stimulate TNF-alpha production. 3) The synergistic effect of bleomycin/SP-A, either before or after oxidation, can be inhibited to the level of bleomycin alone by surfactant lipids. 4) Differences in oligomerization were also observed between SP-A1 and SP-A2. The results indicate that differences among SP-A variants may partly explain the individual variability of pulmonary complications observed during bleomycin chemotherapy and/or in an environment that may promote protein oxidation.

Surfactant protein A (SP-A) plays a role in host defense and inflammation in the lung. In the present study, we investigated the hypothesis that SP-A is involved in bleomycin-induced pulmonary fibrosis. We studied the effects of human SP-A on bleomycin-induced cytokine production and mRNA expression in THP-1 macrophage-like cells and obtained the following results. 1) Bleomycin-treated THP-1 cells increased tumor necrosis factor (TNF)-alpha, interleukin (IL)-8, and IL-1beta production in dose- and time-dependent patterns, as we have observed with SP-A. TNF-alpha levels were unaffected by treatment with cytosine arabinoside. 2) The combined bleomycin-SP-A effect on cytokine production is additive by RNase protection assay and synergistic by enzyme-linked immunosorbent assay. 3) Although the bleomycin effect on cytokine production was not significantly affected by the presence of surfactant lipid, the additive and synergistic effect of SP-A-bleomycin on cytokine production was significantly reduced. We speculate that the elevated cytokine levels resulting from the bleomycin-SP-A synergism are responsible for bleomycin-induced pulmonary fibrosis and that surfactant lipids can help ameliorate pulmonary complications observed during bleomycin chemotherapy.

Ozone exposure can cause inflammation and impaired lung function. Human surfactant protein A (SP-A) may play a role in inflammation by modulating cytokine production by macrophages. SP-A is encoded by two genes, SP-A1 and SP-A2, and several allelic variants have been characterized for each gene. These allelic variants differ among themselves in amino acids that may exhibit differential sensitivity to ozone-induced oxidation and this may produce functional differences. We studied the effects of SP-A variants before and after ozone exposure on the production of tumor necrosis factor (TNF)-alpha and interleukin (IL)-8. These are important proinflammatory cytokines and are expressed by the macrophage-like THP-1 cells. Eight variants were expressed in vitro, characterized by gel electrophoresis, and studied. These included six single-gene SP-A alleles and two SP-A variants derived from both genes. Variants were exposed to ozone at 1 ppm for 4 hr at 37 degrees C, and we compared their ability to stimulate cytokine (TNF-alpha and IL-8) production by THP-1 cells to air-exposed and unexposed SP-A variants. We found that a) SP-A2 variants (1A, 1A(0), 1A(1) stimulate significantly more TNF-alpha and IL-8 production than SP-A1 variants (6A, 6A(2), 6A(4); b) coexpressed SP-A variants (1A(0)/6A(2), 1A(1)/6A(4) have significantly higher activity than single gene products; c) after ozone exposure, all SP-A variants showed a decreased ability to stimulate TNF-alpha and IL-8 production, and the level of the decrease varied among SP-A variants (26-48%); and d) human SP-A from patients with alveolar proteinosis exhibited a minimal decrease (18% and 12%, respectively) in its ability to stimulate TNF-alpha and IL-8 after in vitro ozone exposure. We conclude that biochemical and functional differences exist among SP-A variants, that ozone exposure modulates the ability of SP-A variants to stimulate cytokines by THP-1 cells, and that SP-As from bronchoalveolar lavage (BAL) fluid of certain alveolar proteinosis patients may be oxidized in vivo.

Background: Sweet's syndrome (SS), acute febrile neutrophilic dermatosis, has been linked to hematologic malignancies and presents with characteristic edematous dermal plaques. Peripheral blood neutrophilia is frequently seen in association with SS and is one of the diagnostic criteria., Objective: To report the clinical, laboratory, and hematologic data of four patients with myeloid leukemia who developed SS after chemotherapy. Three of these patients were neutropenic., Methods: A retrospective study of four patients with SS and hematologic malignancies was undertaken. Three patients had de novo acute myelogenous leukemia and one was in the acute blast crisis of chronic myelogenous leukemia., Results: Sweet's syndrome was not originally suspected in these patients because of the low peripheral white blood cell counts caused by chemotherapy. All of the patients presented with fevers, arthralgias, and an eruption. They had been treated with antibiotics because of a presumed infection. Once the correct diagnosis was made and oral prednisolone was started, a rapid response followed., Conclusions: Sweet's syndrome should be considered in the differential diagnosis when acute myeloid leukemic patients develop skin lesions and unexplained fevers regardless of the peripheral blood counts.

Thromboembolism is a serious complication of prolonged use of intracirculatory devices such as total artificial hearts (TAH) and ventricular assist devices. The authors have evaluated alteration in the hemostatic system associated with long-term use of TAH and ventricular assist devices. This article reports results of a prospective evaluation of the fibrinolytic system in four calves implanted with TAHs and four with ventricular assist devices. Blood fibrinolytic activity measured with a solid phase radiometric assay was elevated in two of four TAH calves; plasma plasminogen activity was increased in three. Plasma plasminogen activator activity was undetectable (normal) in all animals. Slight to moderate hypofibrinogenemia was noted in all TAH calves. Calves implanted with a left ventricular assist device had mostly normal blood fibrinolytic activity, fibrinogen, and plasminogen levels. Fibrinogen survival was measured in two calves with ventricular assist devices and three with TAH and was in the normal range in all of these animals. No significant thrombotic lesions were noted at autopsy in five calves that died or were electively killed. These observations suggest enhanced activation of the fibrinolytic system in some calves implanted with a TAH. This may offer a measure of protection against thrombosis in some animals.

The two main ingredients of blood clots formed on artificial surface are platelets and fibrinogen. In this study, we measured platelet and fibrinogen survival in calves implanted with total artificial heart (TAH) and left ventricular assist device (LVAD), and correlate these data with autopsy findings. Platelet survival with autologous 111In-labeled platelets was performed on nine calves implanted with TAH and five with LVAD. Fibrinogen survival with 131I-labeled homologous fibrinogen was performed on six calves with TAH and three with LVAD. Platelet survival was significantly shortened in both groups of animals: 5.89 +/- 0.52 days, control 6.46 +/- 0.31 days, p = 0.0013; fibrinogen survival was normal: 8.79 +/- 1.20 days, control 8.64 +/- 1.16 days. At autopsy two calves with TAH had multiorgan thromboembolism. Two other animals with TAH and four with LVAD had focal renal infarcts. Most animals had minor clot formation within the prosthetic device. Major septic complications occurred in four calves with TAH and one with LVAD. Continuous platelet activation by artificial surface probably explains the shortened platelet survival and thromboembolic complications.

The two most serious complications associated with long-term use of a total artificial heart (TAH) are thromboembolism and infection. In this article, we review our experience in one patient implanted with a pneumatic TAH for 396 days, and in 24 calves implanted with the same type of device for 70 to 353 (median 150) days. During his survival with the TAH, our patient suffered several thromboembolic episodes despite adequate anti-coagulation with warfarin. Autopsy showed widespread thrombotic lesions, mostly in the brain. Throughout his survival, the patient had markedly elevated plasma beta-thromboglobulin and fibrinopeptide A levels, indicating sustained activation of platelets and the coagulation system secondary to blood contact with the artificial surface. Long-term use of TAH in calves causes significant mechanical hemolytic anemia and a small reduction in the total leukocyte and neutrophil counts. The platelet count normalized to preimplantation levels by 25 to 35 weeks. At autopsy, thrombotic lesions and organ infarction were noted in 13 calves, and major septic complications were documented in 10 animals. Although impressive gains in the clinical and experimental use of TAH were achieved during the last 15 years, thromboembolism and infection remain challenging problems.

Hemostatic abnormalities are common in patients with metastatic malignancy and are attributed, in part, to materials secreted by tumor cells. Tumor stimulation might therefore cause further perturbation of hemostasis. This article reports observations on the effects of androgen stimulation on multiple hemostatic parameters in patients with metastatic prostate cancer. Testosterone was given before chemotherapy in an experimental protocol designed to increase tumor sensitivity to cytotoxic agents. The following parameters were measured on day 0 (before) and days 2 and 4 of fluoxymesterone administration: PT, APTT, platelet count, plasma betathromboglobulin (BTG), platelet factor 4 (PF4), fibrinogen, fibrin(ogen) split products (FSP), factor VIII coagulant activity (VIII C), von Willebrand factor antigen (vWF Ag), fibrinopeptide A (FPA), antithrombin III (AT III), and protein C antigen (PC). Ten patients were studied during 17 cycles of hormonal stimulation. Baseline levels of BTG, PF4, fibrinogen, FSP, factor VIII C, vWF Ag, and FPA were significantly elevated compared with normal control. Although androgen stimulation resulted in elevation of BTG, FPA, and FSP levels by day 4 in many patients, the changes for the entire group were not statistically significant. Other parameters remained unchanged or were only slightly elevated. Two patients developed laboratory evidence of disseminated intravascular coagulation (DIC) but were clinically unaffected. Our data suggest that most patients with metastatic prostate cancer show evidence of ongoing activation of platelets, coagulation, and fibrinolysis. In a few individual patients, androgen stimulation of this hormonally dependent tumor may cause further activation of platelets, coagulation, and fibrinolysis.

Three patients with acute lymphoblastic leukemia and one with lymphosarcoma cell leukemia developed transient hypofibrinogenemia during a course of treatment with vincristine and prednisone. There was no evidence of overt, disseminated intravascular coagulation or significant liver impairment. Fibrinogen survival using homologous-125-I-labelled fibrinogen was measured in two patients; it was moderately shortened in both, perhaps indicating subclinical intravascular coagulation. Rapid lysis of leukemic cells might have been responsible for activating coagulation and fibrinolysis in vivo. These four patients, however, were not different in any clinical or laboratory parameter from nine others with lymphoblastic leukemia similarly treated and investigated without observing any defect in their fibrinogen. There were no bleeding complications and the fibrinogen level became normal within 13 to 30 days.

Serial T-cell subsets and platelet counts were determined in a cohort of 84 hemophiliacs in whom time of seroconversion for human immunodeficiency virus (HIV) antibody could be ascertained. An abrupt decrease in the number of T-helper (T4) cells was seen in 9 patients 12 to 24 months before the acquired immunodeficiency syndrome (AIDS) was diagnosed (p = 0.0007 compared with those who did not develop AIDS). Thrombocytopenia also was associated with an increased risk for AIDS (p = 0.02), as was older age at the time of seroconversion (p = 0.03). Ten patients developed AIDS at 24 to 95 months after seroconversion, for a cumulative incidence (+/- SE) of 18.0% +/- 7.1% at 6 years. Hemophiliacs who had T4 cell counts of less than 200 cells/microL had a 50% +/- 16% cumulative incidence of AIDS within 2 years, indicating that decreasing or very low T4 cell counts have predictive value for the development of AIDS. Furthermore, the data suggest that thrombocytopenia and older age may be markers for a cofactor that increases the risk for AIDS in hemophiliacs.

Hypofibrinogenemia and disseminated intravascular coagulation are common events in patients with metastatic prostate carcinoma. This study tests the hypothesis that prostate tumor growth and metastasis is associated with sustained activation of fibrinolysis secondary to increased release of plasminogen activator. We implanted an androgen-insensitive prostate tumor into an inbred strain of rats and serially measured plasminogen, plasminogen activator, plasmin and fibrinogen. Control groups included animals without tumor and a group implanted with transitional cell bladder carcinoma, a locally infiltrating tumor not usually associated with hemostatic complications. Our results showed a significant and steady rise in plasma plasminogen activator, plasmin and fibrinogen levels in animals implanted with prostate cancer. This, however, is not specific for prostate tumor. Similar, perhaps more profound changes were noted in animals implanted with the transitional cell carcinoma.

Primary lymphomas of the small intestine (PIL) show definite racial and geographic distribution. Clinical and laboratory data on 132 patients with PIL treated and followed up over a 14-year period in Baghdad, Iraq, are presented. Based on the pattern of involvement of the bowel and the histopathologic appearance of the tumor, the patients can be divided into three main groups. Ninety-seven patients had diffuse lymphoplasmacytic infiltration affecting large segments of the upper bowel. Abdominal pain, anorexia, weight loss, diarrhea, malabsorption, and clubbing of the fingers are the most common clinical findings. The barium appearance of the small intestine and peroral jejunal biopsy specimens are abnormal in nearly all cases. This clinicopathologic entity has been referred to in the literature as Mediterranean lymphoma (ML). Ten of 34 patients tested had free alpha-heavy chain in the serum. Twenty-three cases had other "Western" variants of lymphoma (18 lymphocytic and 5 plasmacytic). The lesions were localized, occurring most frequently in the lower ileum or ileocecal area. The most common presentation was intestinal obstruction. Twelve children had Burkitt's lymphoma (BL), presenting most commonly with abdominal masses and/or intestinal obstruction. These patients responded poorly to cyclophosphamide, and the disease disseminated early and extensively. None of the patients with the localized lymphomas or BL had free alpha chain in the serum.

Clinical and experimental observations suggest that tumor-induced endothelial cell (EC) injury may be one of several initial events in the establishment of tumor metastases. This work investigates tumor-induced EC injury and the interaction between tumor-damaged EC and platelets. We used cultured bovine EC and extracts of four cultured human malignancies. EC injury was assessed by 51Cr and lactic dehydrogenase (LDH) release. Incubation of EC with melanoma, breast carcinoma or lung carcinoma caused significant LDH and 51Cr release, whereas colon cancer seemed ineffective. Increased adhesion of platelets to tumor-injured EC was noted. These observations indicate that certain varieties of tumor cause EC injury. Adhesion of platelets to tumor-injured EC results in the formation of platelet-tumor thrombi at the endothelial surface, an event that may initiate tumor invasion of the vessel wall.

Clinical and experimental observations have firmly established the concept of a two-way interaction between malignancy and the hemostatic system. On the one hand, certain tumors can activate platelets and the coagulation mechanism in vivo, on the other, a convincing case has been made for the involvement of platelets and fibrin in tumor growth and metastasis. A large number of clinical and experimental studies have been conducted in order to test the efficacy of platelet inhibitors and anticoagulants as adjuvants in the treatment of cancer. Antiplatelet drugs gave variable results, depending on the drug and the tumor system tested. Prostaglandin synthetic pathways by both the host and tumor seem to be an important determinant in the response to platelet function inhibitors. Of the various anticoagulants tested, the coumarin derivatives gave somewhat consistent antitumor effect in certain human and experimental cancer. The antitumor effect of oral anticoagulants does not appear to be a primary drug effect and seems related to their role as vitamin K antagonists. It should be emphasized that although the antitumor potential of antithrombotic agents is a subject of keen interest at the present, their use in treating human cancer is still controversial.

Bleeding remains a serious problem in patients with ventricular assist pumping (VAP). Clinical and hemostatic laboratory data in 24 patients who could not be separated from cardiopulmonary bypass (CPB) at the conclusion of open heart surgery and who underwent VAP for 54 to 610 hours were analyzed. The most important variable that correlated with the occurrence of severe bleeding was the duration of CPB: 5.2 +/- 1.6 hours in 13 patients with excessive bleeding, vs 3.6 +/- 1.1 hours in 11 patients with "acceptable" levels of bleeding (p less than 0.01). Moderate thrombocytopenia occurred in all patients but did not appear to be a major contributing factor to excessive bleeding. Disseminated intravascular coagulation (DIC) occurred in 12 patients, 4 of whom were in cardiogenic shock. DIC also correlated with time on CPB: 5.2 +/- 1.7 hours for patients with DIC, vs 3.7 +/- 1.1 hours for patients without DIC (p less than 0.01). No correlation was noted between the duration of VAP and the occurrence of DIC or bleeding.

The observation that warfarin inhibits the growth and metastasis of certain types of clinical and experimental tumors suggests a role for vitamin K in tumor biology. We have investigated synthesis of vitamin K-dependent proteins in four malignant (lung epidermoid carcinoma, melanoma, colon adenocarcinoma, and breast adenocarcinoma) and three normal (colon epithelium, breast epithelium, and fibroblasts) cell lines of human origin grown in tissue cultures. Our results show the following: 1) Vitamin K-dependent carboxylase activity is present in all of the malignant and normal cell lines studied. 2) The malignant as well as normal cell lines synthesize a family of vitamin K-dependent proteins. Microsomal precursors of these proteins with apparent molecular mass of 74, 62, and 34 kDa are common to all malignant and normal cell lines whereas precursors of higher and lower molecular mass seem to be synthesized by some but not all tumor cell lines. 3) The 74 kDa precursor synthesized by colon carcinoma and breast carcinoma was positively identified as a precursor of protein S.

Five patients with idiopathic thrombocytopenic purpura (ITP) associated with malignant lymphoma are presented, and twelve other cases reported in the literature are reviewed. Thirteen patients (76%) had Hodgkin's disease; two had diffuse histiocytic, one, diffuse mixed lymphoma. Idiopathic thrombocytopenic purpura presented as the sole clinical manifestation of initial or recurrent lymphoma in 10 of 15 cases (67%). The spleen was not palpable even in patients who showed involvement with lymphoma at splenectomy. Three patients were asplenic at the onset of idiopathic thrombocytopenic purpura. Successful therapy of the thrombocytopenia correlated with effective control of the underlying lymphoma. Splenectomy gave favorable results in 9 of 10 cases (90%) and uncovered occult lymphoma in five patients. Chemotherapeutic drugs were successful in seven of 12 trials (58%) and only when the underlying disease was also controlled. The overall prognosis was related to the status of the lymphoma and was not altered by the occurrence of the idiopathic thrombocytopenic purpura.

Because there is mounting evidence that localized intravascular coagulation may contribute to tissue injury following a variety of immunologic events, including immune complex diseases, fibrinogen catabolism was studied in patients with systemic lupus erythematosus to determine factors correlating with accelerated coagulation. 125I-fibrinogen half-life in controls was 90.1+/- 11 hours and the mean SLE half-life was 60.5 +/- 12. SLE patients in complete clinical remission had normal half-lives, but patients with symptomatic clinical disease, including renal disease, had significantly reduced fibrinogen survival. Accelerated fibrinogen consumption also correlated with positive tests for anti-DNA antibodies, but not with hypocomplementemia. These observations support the hypothesis that the coagulation system is activated in patients with immune complex diseases. Further studies are required to define the role, if any, that coagulation may play in causing tissue injury.

Primary small intestinal lymphoma (PSIL) represents a heterogenous group of disorders with variable clinical and pathologic features and a characteristic age, socioeconomic, and geographic distribution. In developed countries, PSIL usually occurs as a localized ileal tumor, shows a bimodal age distribution, and most frequently presents with abdominal pain and obstructive symptoms. Histologically, most of these tumors are diffuse histiocytic, lymphocytic, or undifferentiated lymphomas. Other variants of PSIL, collectively referred to as immunoproliferative small intestinal disease, occur most often among young patients of poor socioeconomic status in Third World countries, mostly in the Middle East and Mediterranean area. They are characterized by involvement of long loops of the upper small intestine and commonly present with abdominal pain, diarrhea, malabsorption, and clubbing of the fingers. A subgroup of these patients shows a serological abnormality with the appearance of part of the alpha heavy chain of IgA in the serum. Histologically, the lesion appears as a dense diffuse lymphoplasmacytic infiltrate of the mucosa of the upper jejenum or duodenum. A form of malignant lymphoma of true histiocytic origin complicates long-standing celiac disease. The contrasting clinical, epidemiological, histopathological, and immunological features of these variants of PSIL raise interesting questions about the pathogenesis of small bowel lymphoma.

The purpose of this study was to assess hematologic abnormalities and thromboembolic complications related to long-term use of the pneumatic artificial heart (PAH). Laboratory data and autopsy findings were analyzed from 24 calves that survived 70-353 (150 +/- 82) days after implantation of a PAH. Compared with baseline levels, the hemoglobin was significantly lower, and the plasma hemoglobin and serum LDH significantly higher, throughout the follow-up period. The platelet count decreased during the first 10-30 weeks, but returned to preoperative levels by week 35. Platelet survival in 4 calves in stable condition was normal, and the leukocyte count and absolute neutrophil count were within normal limits. At autopsy, thrombotic complications and organ infarction were noted in 13 calves, and major septic complications were documented in 10 animals. The authors' observations indicate that thromboembolism and infection are major complications of long-term use of the PAH.