Multiple thrombosis associated with Cytomegalovirus enterocolitis in an immunocompetent patient: a case report

Abstract Background Cytomegalovirus (CMV) is reported to have thrombogenic characteristics that activate factor X in vitro and stimulate the production of factor VIII and von Willebrand factor (vWF). Thrombosis associated with CMV infection is prevalent among immunocompromised patients and predominantly presents as a solitary large thrombus in the deep vein, pulmonary artery, splanchnic arteriovenous ducts, or other similar sites. Multiple thrombi, however, are rarely observed in such cases. Here, we report about an immunocompetent man with multiple microthrombi associated with CMV infection. Case presentation A 72-year-old Japanese man who complained of abdominal pain was hospitalized with multiple colonic stenosis. He was later diagnosed with CMV enterocolitis and treated with ganciclover from Day 27 post-admission. During hospitalization, the patient developed thrombi in his fingers. He was initially treated with anticoagulant therapy (rivaroxaban); however, the therapy was discontinued owing to a prolonged activated thromboplastin time and an elevated international normalized ratio of prothrombin time. Instead, vitamin K and fresh-frozen plasma were administered. Nevertheless, his coagulation profile remained abnormal. Eventually, he developed colonic perforation and had to undergo emergency surgery. An intraoperative specimen showed several microthrombi in the middle and small arteriovenous ducts of his small and large intestines. The patient’s coagulopathy improved preoperatively, and his overall condition improved postoperatively. Since the activation of ADAMTS13 was reduced remarkably, the thrombotic tendency was determined to be a thrombotic microangiopathy-like condition owing to increased vWF. We could not attribute the coagulopathy to any other cause except CMV infection; therefore, we concluded that this was a case of multiple thrombosis associated with CMV. Conclusions We present an extremely rare case of a patient with multiple thrombotic microangiopathy-like microthrombosis caused by CMV infection. Our findings suggest that CMV infection may be considered as a differential diagnosis for immunocompetent individuals who present with thrombosis of unspecified cause.

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Concurrent Spontaneous Sublingual and Intramural Small Bowel Hematoma due to Warfarin Use

Case Reports in Emergency Medicine ◽

10.1155/2015/583869 ◽

2015 ◽

Vol 2015 ◽

pp. 1-3 ◽

Cited By ~ 1

Author(s):

Gül Pamukçu Günaydın ◽

Hatice Duygu Çiftçi Sivri ◽

Serkan Sivri ◽

Yavuz Otal ◽

Ayhan Özhasenekler ◽

...

Keyword(s):

Emergency Department ◽

Small Bowel ◽

Warfarin Therapy ◽

International Normalized Ratio ◽

Fresh Frozen Plasma ◽

Close Monitoring ◽

Observation Unit ◽

Fresh Frozen ◽

Tomography Scan ◽

Frozen Plasma

Introduction. We present a case of concurrent spontaneous sublingual and intramural small bowel hematoma due to warfarin anticoagulation.Case. A 71-year-old man presented to the emergency department complaining of a swollen, painful tongue. He was on warfarin therapy. Physical examination revealed sublingual hematoma. His international normalized ratio was 11.9. The computed tomography scan of the neck demonstrated sublingual hematoma. He was admitted to emergency department observation unit, monitored closely; anticoagulation was reversed with fresh frozen plasma and vitamin K. 26 hours after his arrival to the emergency department, his abdominal pain and melena started. His abdomen tomography demonstrated intestinal submucosal hemorrhage in the ileum. He was admitted to surgical floor, monitored closely, and discharged on day 4.Conclusion. Since the patient did not have airway compromise holding anticoagulant, reversing anticoagulation, close monitoring and observation were enough for management of both sublingual and spontaneous intramural small bowel hematoma.

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Abstract WP304: Prothrombin Complex Concentrate Rapidly Reverses Coagulopathy but does not Alter Mortality in Warfarin Intracerebral Hemorrhage

Stroke ◽

10.1161/str.44.suppl_1.awp304 ◽

2013 ◽

Vol 44 (suppl_1) ◽

Author(s):

Xuemei Cai ◽

Susannah Orzell ◽

Sarah Suh ◽

Linda Bresette ◽

Farzaneh Sorond ◽

...

Keyword(s):

Intracerebral Hemorrhage ◽

Vitamin K ◽

Conventional Therapy ◽

Prothrombin Complex Concentrate ◽

International Normalized Ratio ◽

Fresh Frozen Plasma ◽

Thromboembolic Complication ◽

Complication Rates ◽

Significant Difference ◽

Fresh Frozen

INTRODUCTION: Warfarin-associated intracerebral hemorrhage (wICH) remains the most lethal form of iatrogenic stroke. Conventional therapy with fresh frozen plasma (FFP) and intravenous vitamin K takes up to 30 hrs to normalize the international normalized ratio (INR). Prothrombin complex concentrate (PCC) does not require cross-match and is fast acting. We hypothesized that PCC can rapidly reverse coagulopathy and reduce mortality in wICH. Methods: We identified 130 consecutive adult wICH patients over five years from a prospectively collected database. 33 patients were excluded for death or withdrawal of care within 48 hours of admission and 8 patients were excluded for antecedent head trauma, leaving 89 patients for analysis. Forty patients received FFP and vitamin K (conventional therapy) and 49 received PCC in addition to conventional therapy. We compared 6-month mortality, time to INR normalization, quantity of FFP transfused, and thromboembolic complication rates between the two groups. We used logistic regression to adjust for important confounders. Results: PCC-treated and conventional therapy patients had similar distributions of age, sex, co-morbidities, ICH location, initial blood pressure and INR. PCC-treated patients had a higher incidence of intraventicular hemorrhage (IVH) (67% vs 33%). PCC-treated patients required less FFP (mean 6.8 units vs 3.3 units, p<0.0001) and had faster time to INR normalization (mean 3.8 hrs vs 9.8 hrs, p<0.0001). Incidence of ICH expansion was low in both groups. There was no difference in the incidence of deep venous thrombosis and pulmonary embolism (p=0.236) or troponin elevation (p=0.573). There was no significant difference in 6-month mortality (p=0.437) after adjusting for age, ICH location, ICH volume, and presence of IVH. Conclusions: PCC use in wICH was associated with shorter time to INR normalization and reduced FFP transfusion but was not associated with 6-month mortality in this cohort. There was no difference in thromboembolic complication rates between PCC-treated and FFP and vitamin K treated patients. Prospective trials of PCC are necessary to determine if its use can improve morbidity and mortality in wICH and to identify potential subgroups of wICH patients who may benefit from PCC.

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Feasibility of a Collaborative, Prospective Interdisciplinary Review and Pharmacy-Based Dispensing Process for Prothrombin Complex Concentrate

Annals of Pharmacotherapy ◽

10.1177/1060028017750397 ◽

2018 ◽

Vol 52 (5) ◽

pp. 454-461 ◽

Cited By ~ 3

Author(s):

Maria Stratton ◽

Philip Grgurich ◽

Kurt Heim ◽

Sandra Mackey ◽

Joseph D. Burns

Keyword(s):

Adverse Events ◽

Prothrombin Complex Concentrate ◽

International Normalized Ratio ◽

Fresh Frozen Plasma ◽

Reversal Agent ◽

Before And After ◽

Measured Time ◽

Fresh Frozen ◽

Warfarin Reversal ◽

Practice Methods

Background: Therapeutic options for rapid reversal of vitamin K antagonist therapy include 4-factor prothrombin complex concentrate (PCC4) and fresh frozen plasma (FFP). These agents have unique requirements for preparation, potential adverse effects, and cost-effectiveness considerations. Objective: To retrospectively assess whether our process for collaborative prospective review and pharmacy preparation facilitates timely and safe warfarin reversal with PCC4 as compared with FFP and to compare effectiveness and safety of the agents in practice. Methods: We performed a retrospective, single-center, before and after cohort study of patients requiring warfarin reversal for life-threatening bleeding or urgent invasive procedures over an 18-month period. The primary end point was time from ordering of reversal agent to administration. Secondary end points measured time to therapeutic effect and rates of adverse events. Results: Of 98 patients studied, 72 received FFP, and 26 received PCC4. The median times from ordering to administration of FFP and PCC4 were 69 and 44 minutes, respectively ( P = 0.015). Median time from ordering to end of infusion was significantly shorter for PCC4 compared with FFP (54 vs 151 minutes, respectively; P < 0.0001). In all, 72% of PCC4 patients and 28% of FFP patients achieved the goal international normalized ratio (INR) of ≤1.4 at the first INR check ( P < 0.0001). Adverse reactions occurred in 4% of patients in each group. Conclusion: In routine clinical practice incorporating collaborative prospective review and dispensing from the institution’s pharmacy, PCC4 was associated with faster administration, a higher rate of INR correction, and similar rates of adverse events compared with FFP.

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Activation of human factor VII during clotting in vitro

Blood ◽

10.1182/blood.v65.1.218.218 ◽

1985 ◽

Vol 65 (1) ◽

pp. 218-226 ◽

Cited By ~ 19

Author(s):

LV Rao ◽

SP Bajaj ◽

SI Rapaport

Keyword(s):

Tissue Factor ◽

Glass Tube ◽

Factor Vii ◽

Clotting Factor ◽

Activate Factor ◽

Factor Xii ◽

Factor X ◽

Normal Plasma

Abstract We have studied factor VII activation by measuring the ratio of factor VII clotting to coupled amidolytic activity (VIIc/VIIam) and cleavage of 125I-factor VII. In purified systems, a low concentration of Xa or a higher concentration of IXa rapidly activated 125I-factor VII, yielding a VIIc/VIIam ratio of 25 and similar gel profiles of heavy and light chain peaks of VIIa. On further incubation, VIIa activity diminished and a third 125I-peak appeared. When normal blood containing added 125I- factor VII was clotted in a glass tube, the VIIc/VIIam ratio rose fivefold, and 20% of the 125I-factor VII was cleaved. Clotting normal plasma in an activated partial thromboplastin time (APTT) system yielded a VIIc/VIIam ratio of 25 and over 90% cleavage of 125I-factor VII. Clotting factor XII-deficient plasma preincubated with antibodies to factor X in an APTT system with added XIa yielded a VIIc/VIIam ratio of 19 and about 60% cleavage, which indicates that IXa, at a concentration achievable in plasma, can effectively activate factor VII. Clotting normal plasma with undiluted tissue factor yielded a VIIc/VIIam ratio of 15 to 20 and 60% cleavage of 125I-factor VII, whereas clotting plasma with diluted tissue factor activated factor VII only minimally. We conclude that both Xa and IXa can function as significant activators of factor VII in in vitro clotting mixtures but believe that only small amounts of factor VII may be activated in vivo during hemostasis.

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Inherited Moderate Factor X Deficiency Presenting as Cardiac Tamponade

Case Reports in Hematology ◽

10.1155/2019/9657516 ◽

2019 ◽

Vol 2019 ◽

pp. 1-4

Author(s):

Tamer Othman ◽

Ayman Abdelkarim ◽

Karen Huynh ◽

An Uche ◽

Jennifer Lee

Keyword(s):

Cardiac Tamponade ◽

Clinical Manifestations ◽

Missense Variant ◽

Fresh Frozen Plasma ◽

Factor X ◽

Pericardial Window ◽

Extensive Experience ◽

Management Guidelines ◽

Factor X Deficiency ◽

Fresh Frozen

Factor X deficiency is a rare bleeding disorder that varies in the severity of its clinical manifestations. The symptoms of this disorder can occur at any age, although most severe cases appear in childhood. The rarity of this condition has not allowed for the establishment of evidence‐based management guidelines, and thus, individuals afflicted with factor X deficiency are treated based on limited literature and the opinions of clinicians with extensive experience. In this case report, we discuss a unique presentation of a 38-year-old male who was found to have cardiac tamponade as a result of his newly diagnosed inherited moderate factor X deficiency. This was discovered by obtaining a factor X activity assay and confirmed with genetic testing which demonstrated a missense variant on the factor X gene on chromosome 13. His management involved correction of his factor X deficiency with fresh frozen plasma, a pericardiocentesis, and placement of a pericardial window. He has been asymptomatic and without hemorrhagic episodes for the 10 months following his discharge.

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Fibrinogen concentrate and cryoprecipitate but not fresh frozen plasma correct low fibrinogen concentrations following in vitro haemodilution

Thrombosis Research ◽

10.1016/j.thromres.2013.02.009 ◽

2013 ◽

Vol 131 (5) ◽

pp. e210-e213 ◽

Cited By ~ 14

Author(s):

Christian Fenger-Eriksen ◽

Kirsten Christiansen ◽

John Laurie ◽

Benny Sørensen ◽

Catherine Rea

Keyword(s):

Fresh Frozen Plasma ◽

Fibrinogen Concentrate ◽

Fresh Frozen ◽

Frozen Plasma

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Predisposing factors for enlargement of intracerebral hemorrhage in patients treated with warfarin

Thrombosis and Haemostasis ◽

10.1055/s-0037-1613443 ◽

2003 ◽

Vol 89 (02) ◽

pp. 278-283 ◽

Cited By ~ 95

Author(s):

Kazuo Minematsu ◽

Hiroaki Naritomi ◽

Toshiyuki Sakata ◽

Takenori Yamaguchi ◽

Masahiro Yasaka

Keyword(s):

Logistic Regression Model ◽

Prothrombin Complex Concentrate ◽

Warfarin Therapy ◽

International Normalized Ratio ◽

Fresh Frozen Plasma ◽

Predisposing Factors ◽

Predisposing Factor ◽

Fresh Frozen ◽

Cerebral Hematoma ◽

Frozen Plasma

SummaryTo elucidate predisposing factors for enlargement of intra-cerebral hematoma (ICH) during warfarin therapy, we reviewed 47 patients on warfarin who developed acute ICH and determined relationships among ICH enlargement, INR reversal and clinical data. Among 36 patients treated to counteract the effects of warfarin within 24 h of onset, ICH increased in 10 patients (enlarged group), but remained unchanged in the remaining 26 (unchanged group), while ICH remained unchanged in another 11 patients in whom the effect of warfarin was reversed after 24 h. The international normalized ratio (INR) was counteracted immediately in 11 patients treated with prothrombin complex concentrate (PCC) but gradually in the other 36 treated by reducing the dose of warfarin, or by administering vitamin K or fresh frozen plasma. Multivariate analysis with a logistic regression model showed an INR value <2.0 at admission or for 24 h after immediate INR correction with PCC prevented ICH enlargement (OR 0.069, 95%CI 0.006-0.789, p = 0.031). An INR value of >2.0 within 24 h of ICH seems an important predisposing factor for ICH enlargement.

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Preparation of Highly Purified Human Thrombin and Factor Xa in a Simultainous Procedure

10.1055/s-0039-1689646 ◽

1975 ◽

Author(s):

M. Miller-Andersson

Keyword(s):

Specific Activity ◽

Factor Xa ◽

Fresh Frozen Plasma ◽

Factor X ◽

Serum Factors ◽

Human Thrombin ◽

Fresh Frozen ◽

Brain Material ◽

The Brain ◽

Chromatography Step

A preparation procedure that purifies Thrombin and activated factor X in a simultainous process has been worked out. Prothrombin complex was first prepared from fresh frozen plasma by chromatography on DEAE-Sephadex. Prothrombin activator was prepared from human brain thromboplastin and bovine serum factors. The activation was performed at 20° C and followed by assaying thrombin activity. After activation the brain material was removed by centrifugation. The protein mixture was immediately adsorbed on to Amberlite IRC-50 and both enzymes were fully adsorbed to the resin. They were eluted in a CaCl2 gradient and the two enzymes eluted in two slightly owerlapping peaks.The thrombin obtained in this procedure was highly purified with a specific activity of 2100 U per mg protein. The activated factor X contained traces of thrombin. It was fully suitable for anti Xa assays of heparin. When higher degree of purity was needed the activated factor X was further purified in an iron-exchange or affinity chromatography step.

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A Protocol for the Rapid Normalization of INR in Trauma Patients with Intracranial Hemorrhage on Prescribed Warfarin Therapy

The American Surgeon ◽

10.1177/000313480807400919 ◽

2008 ◽

Vol 74 (9) ◽

pp. 858-861 ◽

Cited By ~ 20

Author(s):

Michael Kalina ◽

Glen Tinkoff ◽

Adebayo Gbadebo ◽

Paula Veneri ◽

Gerard Fulda

Keyword(s):

Intracranial Hemorrhage ◽

Prothrombin Complex Concentrate ◽

Warfarin Therapy ◽

International Normalized Ratio ◽

Fresh Frozen Plasma ◽

Operative Intervention ◽

Trauma Patients ◽

Number Of Patients ◽

Fresh Frozen ◽

Factor Concentrate

Trauma patients on prescribed warfarin therapy sustaining intracranial hemorrhage can be difficult to manage. Rapid normalization of coagulopathy is imperative to operative intervention and may affect outcomes. To identify and expedite warfarin reversal, we designed a protocol to administer a prothrombin complex concentrate. A Proplex T protocol was instituted in May 2004. It dictated that trauma patients with an International Normalized Ratio (INR) greater than 1.5, history of prescribed warfarin therapy, and intracranial hemorrhage on CT scan receive a prothrombin complex concentrate for reversal of their coagulopathy. Neither the protocol nor the factor concentrate was validated for use in this subset of trauma patients; therefore, adherence to the protocol and use of the factor concentrate was not mandatory. Patients not administered the prothrombin complex concentrate received vitamin K and fresh-frozen plasma. The protocol resulted in an increased number of patients receiving Proplex T (54.3% vs 35.4%, P = 0.047). Protocol patients had improved times to normalization of INR (331.3 vs 737.8 minutes, P = 0.048), number of patients with reversal of coagulopathy (73.2% vs 50.9%, P = 0.026), and time to operative intervention (222.6 vs 351.3 minutes, P = 0.045) compared with control subjects. There were no differences in intensive care unit (ICU) days, hospital days, or mortality. The Proplex T protocol increased the number of patients who received prothrombin complex concentrate, provided rapid normalization of INR, and improved time to operative intervention.

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Effects of fresh-frozen plasma and its cryosupernatant fraction on von Willebrand factor multimeric forms in chronic relapsing thrombotic thrombocytopenic purpura

Blood ◽

10.1182/blood.v65.5.1232.1232 ◽

1985 ◽

Vol 65 (5) ◽

pp. 1232-1236 ◽

Cited By ~ 79

Author(s):

JL Moake ◽

JJ Byrnes ◽

JH Troll ◽

CK Rudy ◽

SL Hong ◽

...

Keyword(s):

Plasma Exchange ◽

Fresh Frozen Plasma ◽

Plasma Samples ◽

Fresh Frozen ◽

Normal Human ◽

Von Willebrand ◽

Willebrand Factor ◽

Frozen Plasma

Abstract Remission plasma samples of some patients with chronic relapsing thrombotic thrombocytopenic purpura (TTP) contain unusually large von Willebrand factor (vWF) multimers similar to those produced by normal human endothelial cells in culture. The infusion of the cryosupernatant fraction of normal plasma is as effective as normal fresh-frozen plasma (FFP) in the treatment or prevention of TTP episodes in patients with the chronic relapsing form of TTP. Three patients with chronic relapsing TTP during remission have unusually large vWF multimers present in their plasma. Two of the patients were transfused once with FFP, one of the two received cryosupernatant on three occasions, and the third patient was studied before and immediately after plasma exchange. Unusually large vWF multimers decreased or disappeared from patient plasma samples within 1/2 to 1 1/2 hours following the transfusion of FFP (on two occasions) or cryosupernatant (on two of three occasions), and immediately after plasma exchange (on one occasion). The patient who received cryosupernatant was studied serially after the infusions. Unusually large vWF multimers returned to her plasma within ten to 24 hours and persisted thereafter. Unusually large vWF multimers did not disappear from patient remission plasma samples, or from the culture medium removed from normal human endothelial cells, when these fluids were incubated in vitro with either normal FFP or cryosupernatant. We conclude that an activity in FFP, and its cryosupernatant fraction, promoted the rapid in vivo disappearance of unusually large vWF multimers from the plasma of two patients with chronic relapsing TTP in remission, and plasma exchange reversed the abnormality in a third patient who was in partial remission. Neither FFP nor cryosupernatant directly converted unusually large multimers to smaller vWF forms in vitro in the fluid phase. These results indicate that an activity in the cryosupernatant fraction of normal plasma is involved in vivo in controlling the metabolism of unusually large vWF multimers, and that this process is defective in some chronic relapsing TTP patients.

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