Heparin-like Anticoagulant Research Articles

Bleeding Diathesis Secondary to a Heparin-Like Anticoagulant in a Patient with Multiple Myeloma—A Case Report and Review of Literature

AbstractMultiple myeloma (MM) is a clonal plasma cell disorder that commonly presents with anemia, renal failure, hypercalcemia, and lytic bone lesions. MM is also frequently associated with thrombotic complications; however, it may rarely present with bleeding diathesis. We report a case of a 42-year-old gentleman with relapsed immunoglobulin G lambda MM who presented with epistaxis, gingival bleeding, and oozing at the venepuncture site. Routine tests of coagulation revealed a prolonged prothrombin time (PT), activated partial thromboplastin time (aPTT), and thrombin time. The PT and aPTT failed to correct with pooled normal plasma and the patient was thus diagnosed to have an acquired heparin-like anticoagulant (HLAC). The source of this HLAC has long been debated, but recent data have demonstrated that this HLAC may be the paraproteins produced by the malignant plasma cells. The patient was treated with intravenous protamine sulfate, repeated cycles of plasma exchange, and a daratumumab-based quadruplet regimen but eventually succumbed to an intracranial hemorrhage. HLAC is a rare but potentially fatal complication of MM that must be considered when patients with MM present with bleeding diathesis.

Fatal Bleeding Due to a Heparin-Like Anticoagulant in a 37-Year-Old Woman Suffering From Systemic Mastocytosis

A 37-year-old female patient with systemic mastocytosis who was admitted with severe unexplained bleeding symptoms is studied. Laboratory procedures established the diagnosis of a patient-derived-heparin-like anticoagulant as a very rare hemostatic abnormality predisposing to bleeding. The patient died from refractory disease despite therapy with protamine, initiation of chemotherapy, and supportive measures. The case illustrates the clinical presentation and diagnosis of heparin-like anticoagulants. Etiology, pathophysiology, and therapeutic options are discussed.

A Novel Congenital Bleeding Disorder Related to High Plasma Heparin-Like Anticoagulant Activity.

Heparin or heparin-like compounds present in human plasma in minute amounts. It has been reported that a very few patients with such diseases as plasma cell neoplasms, acute monoblastic leukemia and acquired immune deficincy syndrome have an increased plasma heparin-like anticoagulant activity. Recently, we found a 10-year-old girl who was physically and developmentally normal, but had recurrent episodes of prolonged bleeding and hematoma starting in her early childhood, which could be stopped by transfusion of fresh frozen plasma or prothrombin complex concentrate. The coagulation tests of her plasma were regularly repeated since she was 2 years old, and always revealed a markedly prolonged APTT (61.8–104 seconds, normal 28–40 seconds) and TT (36–50.1 seconds, normal 14–21 seconds), and a slightly prolonged PT (15.9–25 seconds, normal 11–14.5 seconds). Fibrinogen, prothrombin and other coagulation factors as well as anticoagulant and fibrinolytic systems were all normal. The results of immunologic measurements were either negative or within normal ranges. Treatment of the patient's plasma in vitro with either protamine or heparinase could completely normalize the coagulation abnormalities, but not with normal plasma. The anticoagulant activity of her plasma corresponded to 0.2 heparin U/mL when measured by a TT assay using normal plasma as substrate and standardized with porcine heparin. Her plasma heparin concentration was 0.22 heparin U/mL when measured using a colometric assay. In ex vivo study, the abnormal coagulation tests could effectively be corrected when the patient was intravenously administed with protamine. Considering these characteristic laboratory features of the patient, we suppose it would probably represent a novel congenital bleeding disorder related to high plasma heparin-like anticoagulant activity which, to our knowledge, had not been described before.

Acquired heparin-like anticoagulants: a second case in metastatic breast carcinoma and literature review

We report the second case of an acquired heparin-like anticoagulant in a patient with disseminated breast carcinoma. All but one of the small numbers of other cases have also been associated with an underlying malignancy. We comment on the distinction between an immunoglobulin and proteoglycan causing the antithrombin effect and suggest points of interest for consideration in any future cases together with a review of treatment options.

Tissue Anticoagulants in the Human Placenta: Preliminary Study with a Heparin-Like Anticoagulant and Review of the Literature

In this study a new heparin-like anticoagulant in the human placenta is described and an extensive review of the literature is given. An anticoagulant with a heparin-like activity was isolated from an extract of the human placenta. A two-stage purification procedure was applied: affinity chromatography on heparin-Sepharose and ion-exchange chromatography on DEAE-trisacryl. The isolated anticoagulant fraction was found to prolong both thrombin clotting time and activated partial thromboplastin time and to increase the activity of antithrombin III and heparin cofactor II. The placental-tissue anticoagulants described in the literature are divided by the author into five groups: (1) acidic peptides of low molecular weight; (2) thrombomodulin; (3) phospholipid-binding protein anticoagulants; (4) heparin-like anticoagulants, and (5) others. The anticoagulant described in the present study has been classified to the 4th group.

Heparin-Like Anticoagulant Associated with AIDS

Heparin-Like Anticoagulant Associated with AIDS

Heparin-Like Anticoagulant Associated with Plasma Cell Myeloma

A 54-year-old man with plasma cell myeloma had sustained bleeding develop after prophylactic hip hemiarthroplasty. Routine coagulation studies revealed significant prolongation of the prothrombin time, activated partial thromboplastin time, and thrombin time. Further evaluation showed failure of the activated partial thromboplastin time to correct in a 1:1 mixture with pooled normal plasma, correction of the prolonged thrombin time by addition of protamine, and a normal reptilase time. A purified preparation of the immunoglobulin component of patient plasma produced the same pattern of coagulation abnormalities, suggesting the paraprotein possessed heparin-like anticoagulant activity. This appears to be a rare mechanism of bleeding diathesis in plasma cell myeloma.

Intravascular Coagulation with Generalized Shwartzman Reaction Induced by a Heparin-Like Anticoagulant (Liquoid)

SummaryLiquoid (sodium polyanethol sulfonate), a synthetic heparin-like anticoagulant, produces renal cortical necrosis in rabbits. This lesion is indistinguishable from the generalized Shwartzman reaction which is caused by intravascular coagulation in a prepared animal. We have investigated this apparently paradoxic effect of Liquoid. Our main findings are:1. Liquoid is a potent heparin-like anticoagulant. One mg of Liquoid is neutralized by 1 mg of Polybrene. After intravenous injection the anticoagulant effect is immediate and persists for several hours.2. In larger concentrations, Liquoid precipitates fibrinogen. The precipitation does not depend on an intact coagulation system; the precipitates are dissolved in 30% urea.3. An intravenous injection of 20 mg Liquoid/1500 g body-weight produces an early thrombocytopenia, a progressive depletion of fibrinogen and factor V, the appearance of cold-precipitating material in plasma, and severe renal cortical necrosis.4. Pretreatment with warfarin completely prevents all of these effects, except a moderate fall in platelets.We conclude that Liquoid produces these effects, not by precipitation of fibrinogen, but by intravascular coagulation, probably released through aggregation and damage of the platelets. Thus, intravascular coagulation is again confirmed as the final event in the generalized Shwartzman reaction.

A puerperal haemorrhagic state due to a henarin-like anticoagulant.

The occurrence of a severe generalized haemorrhagic state in an obstetric case due to a heparin-like anticoagulant is described. This appeared in the post-partum period apparently following a compatible blood transfusion. The pattern of results found in conventional laboratory tests for elucidating acute blood coagulation disorders is described, and the distinction between heparinaemia and the defibrination syndrome emphasized. Protamine sulphate corrected the clotting abnormality in vitro and when administered in amounts so as to achieve a similar concentration in vivo was followed by correction of the blood coagulation and the sudden cessation of bleeding from multiple sites.

THE LOCALIZATION OF HEPARIN-LIKE BLOOD ANTICOAGULANT SUBSTANCES IN THE TISSUES OF SPISULA SOLIDISSIMA

1. A heparin-like blood anticoagulant has been isolated from the surf clam Spisula solidissima.2. The most potent preparation obtained had an anticoagulant activity of 130 U.S.P. heparin units per milligram and was derived from mantle tissue.3. Anticoagulant assays made on tryptic digests from various portions of the clam revealed that the mantle, gills and palps had about five times more anticoagulant activity per gram of tissue than the foot and adductor muscles. It was also found that the eggs of Spisula yield a high anticoagulant activity.4. Toluidine blue staining of sectioned eggs revealed metachromasia in the jelly coat, cortical region and nucleolus.5. In order to determine the origin of the anticoagulant from the adult clam, the results from anticoagulant assays made on digests of isolated portions of the mantle edge were compared with histologic observations concerning metachromasia. It was concluded that at least two substances with heparin activity are present in the mantle tissue. One of thes...