Coagulation Abnormalities In Patients Research Articles

Managing Coagulation Abnormalities in Patients with Cirrhosis

Liver-related acquired coagulation disorders in patients with cirrhosis are poorly understood. Growing evidence suggests that these patients maintain a

The role of hypercoagulability in the development of osteonecrosis of the femoral head

Despite the large number of the outstanding researches, pathogenesis of osteonecrosis remains unknown. During the last decades the hypothesis that increased intravascular coagulation may be the pathogenetic mechanism which leads to osteonecrosis is gaining constantly support. Both primary factors of hyper-coagulability, such as resistance to activated protein C, protein C and protein S deficiency, low levels of tissue plasminogen activator, high levels of plasminogen activator inhibitor, von Willebrand factor, lipoprotein (a), and secondary factors of hypercoagulability with factors potentially activating intravascular coagulation, such as pregnancy, antiphospholipid antibodies, systemic lupus erythematosus, hemoglobinopathies and sickle cell disease, and hemato-oncologic diseases are discussed in this article. Although coagulation abnormalities in patients with hip osteonecrosis might represent increased risk factors for the development of bone necrosis by predisposing the patient to thromboembolic phenomena, further investigation is needed to indicate the definite correlation between factors leading to increased intravascular coagulation and pathogenesis of osteonecrosis.

Dysregulated coagulation associated with hypofibrinogenaemia and plasma hypercoagulability: Implications for identifying coagulopathic mechanisms in humans

Identifying coagulation abnormalities in patients with combined bleeding and thrombosis history is clinically challenging. Our goal was to probe the complexity of dysregulated coagulation in humans by characterizing pathophysiologic mechanisms in a patient with both bleeding and thrombosis. The patient is a 56-year-old female with a history of haematomas, poor wound healing, and thrombosis (retinal artery occlusion and transient cerebral ischaemia). She had a normal activated partial thromboplastin time, prolonged thrombin and reptilase times, and decreased functional and antigenic fibrinogen levels, and was initially diagnosed with hypodysfibrinogenaemia. This diagnosis was supported by DNA analysis revealing a novel FGB mutation (c.656A>G) predicting a Q189R mutation in the mature chain that was present in the heterozygote state. However, turbidity analysis showed that purified fibrinogen polymerisation and degradation were indistinguishable from normal, and Bβ chain subpopulations appeared normal by two-dimensional difference in-gel electrophoresis, indicating the mutated chain was not secreted. Interestingly, plasma thrombin generation testing revealed the patient's thrombin generation was higher than normal and could be attributed to elevated levels of factor VIII (FVIII, 163-225%). Accordingly, in an arterial injury model, hypofibrinogenaemic mice (Fgn(+/-)) infused with factor VIII demonstrated significantly shorter vessel occlusion times than saline-infused Fgn(+/-) mice. Together, these data associate the complex bleeding and thrombotic presentation with combined hypofibrinogenaemia plus plasma hypercoagulability. These findings suggest previous cases in which fibrinogen abnormalities have been associated with thrombosis may also be complicated by co-existing plasma hypercoagulability and illustrate the importance of "global" coagulation testing in patients with compound presentations.

Cerebral Infarction Developing in A Patient Without Cancer With A Markedly Elevated Level of Mucinous Tumor Marker

Previous studies have shown the possible role of mucin in cerebral infarction associated with coagulation abnormalities in patients with cancer, particularly adenocarcinoma. We report a 42-year-old woman who developed motor aphasia and cerebral infarction in the left frontal lobe and right parietal lobe. A mucinous tumor marker, CA125 level, was markedly elevated at 1750 U/mL (normal, <36 U/mL), and the D-dimer level was 6.0 μg/mL (normal, <1 μg/mL). She had adenomyosis and no malignancy was revealed. The CA125 and the D-dimer levels became normal after treatment of adenomyosis. Our findings suggest for the first time that marked elevation of mucinous tumor marker level may cause cerebral infarction even in benign conditions.

Periprosthetic Joint Infection Can Cause Abnormal Systemic Coagulation

Surgery may often be needed for treatment of patients with a periprosthetic joint infection (PJI). This study intended to evaluate the incidence of abnormal coagulation and determine the efficacy of treatment of reversing a coagulation abnormality in patients with PJI. The cohort included 294 patients undergoing treatment of PJI at our institution from 1998 to 2005. In our final analysis, 72 patients (56%) had abnormal coagulation (defined as international normalized ratio >1.12). Fresh frozen plasma and/or vitamin K were administered to 29 of these patients (40%). The international normalized ratio was normalized in only 7 (24.1%) of the latter patients. It appears that more than one half of patients with PJI may have abnormal coagulation even without being exposed to anticoagulation agents, highlighting the possibility that patients with PJI may have circulating levels of biologically active agents that affect coagulation.

The Timing of Expression of Blood Coagulation Abnormality in Patients Treated with Warfarin and S-1 Concomitantly

Although S-1 is frequently used in cancer chemotherapy, the drug interaction with warfarin, an anticoagulant agent, is not fully paid attention. In the present study, we investigated retrospectively the timing of expression of blood coagulation abnormality in nine patients treated with warfarin and S-1 concomitantly. In five patients, the dose of warfarin was reduced or interrupted after concomitant use of S-1. The International Normalized Ratio (INR) was significantly increased after combination with S-1 compared with the former value. In all patients, the INR was increased in three weeks after combination with S-1. On the other hand, serum creatinine, aspartate aminotransferase, alanine aminotransferase or serum albumin was not different before and after combination with S-1. These results suggest that the careful monitoring of the blood coagulation ability is necessary in all patients receiving warfarin and S-1 concomitantly.

Hypofibrinogenemia in isolated traumatic brain injury in Indian patients

Coagulation abnormalities are common in patients with head injuries. However, the effect of brain injury on fibrinogen levels has not been well studied prospectively to assess coagulation abnormalities in patients with moderate and severe head injuries and correlate these abnormalities with the neurologic outcome. Consecutive patients with moderate (Glasgow Comma Scale (GCS),9-12) and severe (GCS≤8) head injuries were the subjects of this pilot study, All patients had coagulation parameters, including plasma fibrinogen levels measured. Clinical and computed tomography (CT) scan findings and immediate clinical outcome were analyzed. Of the 100 patients enrolled, only seven (7%) patients had hypofibrinogenemia (fibrinogen ≤200 mg/dL). The head injury was moderate in two patients and severe in five patients. Fibrinogen levels showed a progressively increasing trend in four patients (three with severe head injuries and one with moderate head injury). CT scan revealed subdural hematoma in five patients; extradural hematoma in one; and subarachnoid hemorrhage in another patient. Of the seven patients, two patients died during hospital. Large-scale prospective studies are needed to assess the fibrinogen level in patients with head injury and its impact on outcome.

Hemoperfusion With a Polymyxin B Fiber Column Decreases Clotting Activity

We investigated whether hemoperfusion with a polymyxin B column (DHP-PMX) was able to improve coagulation abnormalities in patients with sepsis. Sixteen patients with sepsis were enrolled in the study. They all had signs of systemic inflammatory response syndrome due to infection and a mean arterial blood pressure > or =65mm Hg (irrespective of the use of catecholamines). A thermodilution catheter was inserted prior to DHP-PMX for intravenous infusion, and DHP-PMX was performed twice within 24 h for 3 h each time. Circulating levels of thrombin-antithrombin complex (TAT), plasmin-alpha2 plasmin inhibitor complex (PIC), the TAT/PIC ratio, and plasminogen activator inhibitor-1 (PAI-1) were measured six times. Before DHP-PMX, the TAT level was 24.5 +/- 8.3 ng/mL, the PIC level was 2.5 +/- 1.1 microg/mL, the TAT/PIC ratio was 13.9 +/- 3.5, and the PAI-1 level was 143.0 +/- 24.4 ng/L. The TAT level, TAT/PIC ratio, and PAI-1 were all significantly lower (P < 0.05) after 48 hr compared with before DHP-PMX, but no significant change of PIC was observed. In these patients with sepsis, fibrinolysis was inhibited by PAI-1, whereas clotting activity was significantly increased. This coagulation/fibrinolysis imbalance was improved by DHP-PMX. The present results suggest that indirect inhibition of clotting activity can be achieved in patients with sepsis through adsorption of lipopolysaccharide by DHP-PMX.

Thrombophilic patterns of coagulation factors in lupus

Our aim was to better define the coagulation abnormalities in patients with systemic lupus erythematosus who had thrombosis or high-risk clinical settings for thrombosis. Clinical and laboratory data of 111 patients with lupus referred for coagulation assessment because of thrombosis, pregnancy loss or high-risk clinical settings for thrombosis were reviewed retrospectively. Increased activity of procoagulant factors and decreased activity of anti-coagulant factors were observed well above the expected 5% prevalence. All comparisons were significant at the P < 0.001 level. Anticardiolipin antibodies were present in 70.5% of patients tested (55/78) in this high-risk group, but usually in low titres. Platelet hyperfunction was detected in the majority of patients tested (85.7%, 78/91). Hypercoagulability in lupus is complex and is better defined by assessing multiple haemostatic factors in addition to platelet function. Platelet hyperfunction contributes significantly to thrombophilia in lupus and this is the key finding of our study.

Prothrombotic Coagulation Abnormalities in Patients with Paraprotein-Producing B-Cell Disorders

PurposeAn increased incidence of thromboembolic complications has been observed in multiple myeloma (MM), especially when patients are treated with anthracycline-based chemotherapy. In patients with MM, plasma levels of several prothrombotic coagulation factors are increased, and this can contribute to the prothrombotic state of these patients. Recently, an increased thrombosis risk has also been described for other plasma cell disorders (PCDs), such as monoclonal gammopathy of uncertain significance (MGUS) and systemic amyloidosis. The aim of this study was to analyze prothrombotic coagulation disorders in patients with paraprotein-producing B-cell disorders, such as MGUS, systemic amyloidosis, Waldenström's macroglobulinemia, and MM. Patients and MethodsAn increase in factor VIII and von Willebrand factor was observed in patients with MGUS and systemic amyloidosis that was similar to increases seen in patients with untreated MM. The highest levels were observed in patients with systemic amyloidosis. ResultsWe observed several coagulation abnormalities in patients with different PCDs. ConclusionThese prothrombotic changes in patients with MM, systemic amyloidosis, and Waldenström's macroglobulinemia might be causally related to the observed incidence of venous thromboembolism in these forms of PCDs.

Coagulation abnormalities in patients with metastatic colon cancer on bevacizumab therapy

14578 Background: Bevacizumab (Avastin) is a recombinant humanized monoclonal antibody to vascular endothelial growth factor (VEGF) that functions as an anti-angiogenic agent. VEGF is a glycoprotein, important for regulation of angiogenesis in normal and pathologic cells and is required for the maintenance of immature blood vessels, found in tumors. In addition to direct antiangiogenic effects, bevacizumab improves chemotherapy delivery by altering tumor vasculature as well as decreasing the size and number of liver tumors in mouse xenograft model of human colon cancer metastases. This study aimed to look for predictors of the development of major toxicities such as bleeding and clotting that would increase the incidence of such events in patients with metastatic colorectal carcinoma on Bevacizumab therapy. Methods: The study was a retrospective analysis over the past 2 years, reviewing the charts of 59 successive patients receiving bevacizumab in our institution. Particular emphasis was placed on age, gender, tumor type and location, location of metastases, chemotherapy regiment/number of cycles, past medical history, hemoglobin/hematocrit values, PT/INR values, liver function tests and albumin values at the time of the diagnosis and event. Utilizing univariant and multivariant analysis the goal was to determine contributing risk factors for increased incidence of bleeding and clotting. Results: 20.3% of the patients were found to have a major complication, such as clotting or bleeding. Once analyzed, there were four statistically significant indicators (p &lt; 0.05) that predicted for the incidence of either one of the events. They included older patient age, low albumin values at the time of the event (as defined by the institution value of less than 3.6), location of the tumor (cecum, ascending colon and sigmoid colon were predominant), and the site of the metastasis (liver and lung). Conclusions: Clotting and bleeding complications in patients on Bevacizumab are not uncommon. It is clear that age, low albumin values, metastatic site and tumor location contribute to an increased incidence of such events in patients with metastatic colon cancer on Bevacizumab therapy. [Table: see text]

Prothrombotic coagulation abnormalities in patients with newly diagnosed multiple myeloma

Prothrombotic coagulation abnormalities were analyzed in patients with untreated multiple myeloma. Increases in factor VIII, in von Willebrand factor (vWF) and a decrease in protein S were observed and these changes were strongly associated with disease stage. No difference in baseline coagulation parameters was found between patients with and without subsequent venous thromboembolism.

A Retrospective Study of Coagulation Abnormalities in Patients Receiving Concomitant Capecitabine and Warfarin

The extent and complications of the interaction between capecitabine and warfarin are not fully known. A retrospective study of 77 patients who received capecitabine was performed to analyze coagulation abnormalities with or without warfarin. Twenty-one patients received warfarin with capecitabine. Twelve were on an average warfarin dosage of 19.4 mg per week (range, 7-35 mg) before capecitabine treatment, with a stable international normalized ratio (INR; range, 0.9-3.3). The dose of capecitabine ranged from 1.6 g/m2 to 2 g/m2 per day. Thirteen patients (11 on warfarin) had an INR > 3 (range, 3.23-11.5), resulting in a probability of an INR > 3 of 32% in the warfarin group versus 4% for those not on warfarin (P = 5.1 x 10(-14)) at 130 days. Six patients required a warfarin dose reduction (1-2.5 mg decrease). There were 7 episodes of bleeding (all gastrointestinal; 5 with warfarin). Seven patients who experienced bleeding had INRs ranging from 1.06 to 8 (average, 3.31) at the time bleeding occurred. Of the 7 bleeding episodes, 5 patients required transfusions, averaging 3.25 units of red blood cells and 2.4 units of fresh frozen plasma. The incidence of bleeding at 130 days of treatment with capecitabine was 18% with warfarin versus 2% without (P = 4 x 10(-13)). Bleeding episodes were not significantly different between patients with or without liver involvement (4 of 40 episodes vs. 3 of 37 episodes, respectively; P = 0.12). Patients with an INR > 3 were evenly distributed between those with or without liver involvement (6 of 40 patients vs. 7 of 37 patients, respectively). No INR increases persisted after discontinuation of capecitabine. This study confirms a clinically significant interaction between warfarin and capecitabine-based chemotherapy akin to that already known for 5-fluorouracil. In addition to altered coagulation parameters, bleeding can be a complication. These events occurred in patients with and without liver metastases. We recommend weekly monitoring of coagulation parameters for all patients receiving concomitant warfarin and capecitabine, with an appropriate adjustment of warfarin dose. The nature and extent of this interaction requires further investigation.

Retrospective analysis of coagulation abnormalities in patients receiving capecitabine (CAP) and warfarin (WAR)

8130 Background: CAP is commonly used in GI tumors. Pts with these tumors are often on WAR for atrial fibrillation (AF), DVT, etc. There have been reports of altered coagulation parameters and blee...

Coagulation Abnormalities in Patients with Noonan Syndrome - a Single Centre Case Series.

Noonan syndrome (NS) is an autosomal dominant disorder that includes short stature, characteristic facies, congenital heart defect, webbed neck, and developmental delay. A mutation in the PTPN11 gene can be identified in 50% of patients. A bleeding tendency is included in the phenotypic spectrum, with factor XI deficiency and platelet abnormalities described most frequently. At Winnipeg's Health Sciences Centre, 24 patients with features typical of NS have been studied by the Special Haemostasis Laboratory. Four patients in whom the diagnosis was suspected but not considered definite are also included in this analysis. Clinical complaints included easy bruising (9), epistaxis (2), menorrhagia (1), and a family history of bleeding problems (3). Sixteen patients were referred for investigation following the diagnosis of NS. All 28 patients had coagulation screening tests: 16 patients had an abnormal PT and 12 had an abnormal aPTT. Thrombin time was slightly prolonged in 6 of 23 patients. Reptilase time was normal in 8 patients, and fibrinogen concentration was normal in 20 patients.Factor XI levels were measured in 14 patients, with a mean value of 62% (range 32–99%). Only 2 patients had levels below the normal range. One of 13 patients evaluated for FXII levels was deficient (FXII 25%), and 2 of 19 patients evaluated for FIX levels had mild FIX deficiency (FIX 40 and 49%) without symptomatic bleeding. No other factor deficiencies were identified. Twenty-four patients had determinations of von Willebrand Factor antigen and activity; 2 had results consistent with mild Type 1 von Willebrand Disease.Platelet aggregation studies were done in 22 patients. A variety of abnormalities were noted, with the most frequent being abnormal aggregation with epinephrine (7/22). Dense granule number was decreased in 2 of 7 samples studied by electron microscopy. Lupus anticoagulants were detected in 3 of 13 patients screened. Thrombophilia investigations in 4 patients detected decreased protein S in one patient who had been diagnosed previously with protein S deficiency.This unselected case series, the largest reported to date in the literature, illustrates the heterogeneity of coagulation abnormalities that may occur in NS. Symptoms, when present, were mild, and often did not correlate with laboratory abnormalities. Non-specific platelet aggregation defects were the most commonly identified abnormalities. In contrast to the literature, factor XI deficiency was not prevalent. A specific etiology for the variable bleeding tendency has not yet been identified in NS.

Therapeutic potential of toleragens in the management of antiphospholipid syndrome.

Autoantibodies to beta2-glycoprotein I (beta2GPI) are believed to be the primary cause of coagulation abnormalities in patients with antiphospholipid syndrome (APS). Clinical features include a range of life-threatening thrombotic events and microangiopathies affecting multiple organ systems. Current standard of care relies on long-term, high-intensity anticoagulation and is associated with a high risk for serious bleeding events. The relation between autoantibodies and the pathophysiology of APS is not clearly understood, but numerous in vitro studies have characterized the effects of antiphospholipid autoantibodies on various components of the coagulation cascade, including tissue factor and the protein C pathway. The fine specificity of autoantibodies to beta2GPI is a subject of considerable debate; however, a body of evidence may offer resolution by integrating concepts of antibody affinity and assay sensitivity with carefully designed molecular studies. An investigational new therapy for APS is based on the approach that pathogenic antibodies may be reduced via depletion of circulating autoantibodies and induction of immune tolerance at the B-cell level. Preliminary results from a phase I/II clinical trial with LJP 1082, a B-cell toleragen, indicate the drug was well tolerated and may warrant further development for reduction of thrombotic events in patients with APS.

Coagulation abnormalities in patients with cyanotic congenital heart disease

PATIENTS WITH CYANOTIC congenital heart disease (CCHD) and associated secondary polycythemia are susceptible to develop coagulation abnormalities. Several coagulation defects, including thrombocytopenia,1-5 factor deficiencies,6 fibrinolysis,7 and disseminated intravascular coagulation (DIC),8-10 have been reported in these patients. Given that definitive surgical correction of congenital lesions in neonates involves complex repairs with a long duration of cardiopulmonary bypass (CPB) and multiple extracardiac suture lines, these coagulopathies predispose the patient to increased bleeding and transfusion requirements perioperatively.11 Primary surgery also is done in adults, and sometimes repeat surgery is necessary after a palliative procedure and definitive first surgery during childhood. This adult population also is known to suffer from excessive postoperative hemorrhage.12 It is reasonable to believe that avoiding excessive hemorrhage after cardiac surgery with CPB in these patients is an important factor in improving surgical outcome. Understanding the management of hematologic disorders that accompany CCHD is an important clinical priority for the cardiac anesthesiologist. Therapeutic guidelines have focused primarily on the management of polycythemia; however, other controversies exist. This article presents the pathophysiology of coagulation abnormalities in these patients and current management strategies.

Cerebral venous thrombosis: Incidence in prothrombotic states

Cerebral venous thrombosis (CVT) is a rare clotting event with a highly variable clinical presentation. Local and systemic infections, collagen vascular disorders, malignancies, pregnancy and puerperium, and the use of oral contraceptives (OC) have been strongly associated with CVT. It is clear that a minority of individuals with the above conditions develop CVT. Therefore, inherited or acquired prothrombotic states may play a key role in the development of this disease. In recent years, the discovery of new thrombophilic risk factors such as factor V Leiden and the prothrombin gene mutation has contributed to the understanding of the environment-gene interaction in the development of thrombosis. Several studies have found factor V Leiden to be the most common coagulation abnormality in patients with CVT, with a prevalence of 20% to 25%. Immobilization, puerperium, or the use of oral contraceptives, factors considered to increase the risk of developing thromboses, were present in the majority of the cases. The odds ratio for CVT in women heterozygous for the prothrombin gene mutation taking OC was 150, with an odds ratio of 10 for carriers of the mutation and 22 for OC users, respectively. Hence, the inherited or acquired hypercoagulable states establish the conditions for thrombosis to develop when certain factors are present. Numerous cases of factor V Leiden and prothrombin gene mutation in patients with CVT during pregnancy and puerperium have been reported, and the prevalence of prothrombotic risk factors appears to be similar to the ones in patients with extracerebral thrombosis during the same period. CVT in neonates and young infants is a rare, but well-recognized disorder with a high morbidity rate. The prevalence of congenital and inherited prothrombotic risk factors in children with CVT is comparable or even higher than in the adult population. Although advances have been made in the characterization of prothrombotic risk factors in patients with CVT, many cases still are considered idiopathic. Larger, well-designed, prospective studies will allow practitioners to determine the population at risk for CVT. Therefore, adequate measures can be taken in order to prevent this severe thrombotic disorder.

Coagulation abnormalities in patients with single-ventricle physiology precede the Fontan procedure

Objective: Thromboembolic events in patients who have undergone the Fontan operation have been reported to be as high as 20% to 33%. A hypercoagulable state with deficiencies in proteins C and S has been implicated. Using age-matched control subjects, we evaluated whether an altered coagulation state is present earlier in the course of staged single-ventricle repair. Methods: After informed consent had been obtained, coagulation factors were assayed in 36 infants (mean age, 7.7 ± 3.6 months) with single-ventricle cardiac defects immediately before undergoing the bidirectional Glenn procedure; 34 infants (mean age, 8.4 ± 2.6 months) without cardiac disease were assayed as control subjects. Concentration of factors II, V, VII, VIII, IX, and X; antithrombin III; plasminogen; proteins C and S; fibrinogen; serum albumin; and liver enzymes were measured. Normal reference intervals on the basis of the control subjects were determined by using 95% confidence limits. Patient demographic and hemodynamic variables were evaluated as possible predictors of coagulation abnormalities. Results: Concentrations of protein C; factors II, V, VII, IX, and X; plasminogen; fibrinogen; and antithrombin III were significantly lower in the pre-Glenn infants compared with in the age-matched control subjects (all P <.001, Student t test). On the basis of multiple logistic regression, no specific hemodynamic variables were predictive of a procoagulant or anticoagulant deficiency. Ventricular dysfunction did predict the presence of multiple coagulation abnormalities (P <.001). Conclusion: Procoagulant and anticoagulant factor abnormalities occur early in the course of single-ventricle repair and precede the cavopulmonary connection.J Thorac Cardiovasc Surg 2002;123:459-65

Livedo (livedoid) vasculitis and the factor V Leiden mutation: Additional evidence for abnormal coagulation

We report the case of a patient with livedo vasculitis associated with the factor V Leiden mutation. This association provides additional support for abnormalities of coagulation in patients with this disorder. The spectrum of platelet, coagulation, and fibrinolytic disorders reported with livedo vasculitis is reviewed. (J Am Acad Dermatol 2002;46:133-7.)