Coagulation Tests In Patients Research Articles

Preoperative D-dimers as an independent prognostic marker in cervical carcinoma.

Activation of coagulation and fibrinolysis has been observed in many tumors. Our study aimed to investigate the clinical and prognostic significance of various plasma coagulation tests in patients with cervical cancer. A total of 296 patients with cervical cancer were included in the analysis. Patients were followed up for at least 60 months until death. Pretreatment parameters including activated partial thromboplastin time, D-dimer, fibrinogen, prothrombin time, thrombin time, lactate dehydrogenase, and squamous cell carcinoma antigen were evaluated. Prothrombin time (hazard ratio = 1.825; P = 0.006) and plasma D-dimer levels (hazard ratio = 2.179; P = 0.036) were identified as significant independent predictors of overall survival. Patients with elevated D-dimer levels had a significantly shorter overall survival compared with those with low-D-dimer levels (<0.5 μg/ml) in the stage I subgroup (n = 98, P = 0.019) and stage II subgroup (n = 77, P = 0.044). D-dimer levels differed significantly according to mortality (P < 0.001), stage I versus stage II (P = 0.030), and stage I versus stage III/IV (P = 0.038). DD level of patients with chemotherapy and/or radiotherapy was higher than patients with other treatment (P < 0.001). Patients with a low-D-dimer level (<0.5 μg/ml) showed a significantly better 5-year overall survival (OS) compared with patients with an increased D-dimer level for different histological typing of squamous cell carcinoma (SCC) (P = 0.001) and non-SCC (P < 0.043). In conclusion, the pretreatment plasma D-dimer level is a potential prognostic factor for cervical cancer.

Clinical Utility of Viscoelastic Tests of Coagulation (TEG/ROTEM) in Patients with Liver Disease and during Liver Transplantation.

The concept that patients with stable liver disease are at an increased risk of bleeding, based solely on abnormalities of conventional coagulation tests such as prothrombin time (PT) and international normalized ratio (INR), is now recognized to be an overly simplistic interpretation of an extremely complex situation. These tests are in fact very poor predictors of bleeding in patients with liver disease who undergo invasive or surgical procedures. Commercially available whole blood viscoelastic tests (thromboelastography [TEG] and thromboelastometry [ROTEM]) evaluate the kinetics of coagulation from initial clot formation to final clot strength. These dynamic tests provide a composite picture reflecting the interaction of plasma, blood cells, and platelets, and more closely reflect the situation in vivo than do PT/INR, which are performed on plasma samples and measure isolated end points. Despite prolonged PT/INR and low platelet counts, viscoelastic tests are within normal range in many patients with both acute and chronic liver disease, commensurate with the concept of rebalanced hemostasis, and in keeping with the fact that an increasing number of these patients undergo liver transplantation without the need for blood or blood products. In addition, these tests reveal important additional information, such as the presence of hypercoagulability and a prothrombotic state, and also information about the presence of endogenous heparinoids associated with vascular endothelial damage, due to sepsis or acute inflammation. This review provides an overview of the current literature on the potential clinical utility of viscoelastic tests of coagulation in patients with liver disease.

Laboratory assessment of warfarin reversal with global coagulation tests versus international normalized ratio in patients with intracranial bleeding.

We assess the in-vivo relationship between international normalized ratio (INR) and global coagulation tests in patients with life-threatening bleeding who received prothrombin complex concentrate (PCC) for warfarin reversal. This was a prospective pilot study in adult patients with intracranial bleeding related to anticoagulation with warfarin. Thromboelastography (TEG), thrombin generation parameters and INR were assessed at baseline, 30 min, 2 and 24 h after PCC. Changes in laboratory parameters and relationship between INR and global coagulation tests were assessed over time. Eight patients mean [standard deviation (SD)] age 72 (16) were included and received mean (SD) dose of PCC 24 (5) units/kg. Four patients died during the study, all with INR values more than 1.5 thirty minutes after PCC. Mean (SD) INR was 3.0 (1.3) and decreased significantly to 1.8 (0.48) thirty minutes after PCC (P < 0.01). Baseline endogenous thrombin potential and thrombin peak were 890 nmol/min and 123 nmol and increased significantly to 1943 nmol/min (P < 0.01) and 301 nmol (P < 0.01) 30 min after PCC administration. Reaction (R)-time decreased significantly (P = 0.02), and maximum amplitude and overall coagulation index (CI) significantly increased during treatment (P < 0.01, respectively). Thrombin generation and TEG values corrected after PCC administration; however, INR did not fully correct. Patients that died tended to be older with prolonged INR values across the study period. INR and TEG values correlated well with thrombin generation before administration of PCC, but this relationship was lost afterward.

Specific and global coagulation tests in patients with mild haemophilia A with a double mutation (Glu113Asp, Arg593Cys).

Heterogeneous bleeding phenotypes are observed in haemophilia A patients with the same mutation in the F8 gene. Specific mutations in the A2 domain of factor VIII are associated with mild haemophilia and a higher risk of inhibitor development. Double mutations in mild haemophilia A are rarely reported. In this study, we investigated the in vitro function of factor VIII, performing different specific and global coagulation assays, observed clinical characteristics and assessed the possible predictive diagnostic value of the differences. The clinical features of haemophiliacs with a mild phenotype were reviewed. Blood samples were obtained and analysed for mutations and coagulation assays: activated partial thromboplastin time, one-stage and chromogenic factor VIII activity, factor VIII antigen and rotational thromboelastometry. We report on a cohort of 22 patients with double Glu113Asp, Arg593Cys mutations. All our patients have a quantitative defect of factor VIII and preserved similar functional activity. Factor VIII activities measured by the one-stage or chromogenic method were not discrepant, although the chromogenic assay resulted in 20% lower factor VIII activities. Waveform analysis showed a lower maximum value of the second derivative curve (Max2) of APTT with curve shape alternation, while thromboelastometry (INTEM) showed low sensitivity in comparison to results in a normal population. In genotyping, the coexistence of a second mutation should never be excluded, especially in cases of discordant clinical presentation. Waveform analysis correlates better with factor VIII activity than thromboelastometry and the Max2 parameter could provide additional information in managing haemophilia patients. The utility of specific factor activity and global haemostatic assays in general practice still needs to be investigated.

Omitting pre-operative coagulation screening tests in hip fracture patients: Stopping the financial cascade?

BackgroundCoagulation screening continues as a standard of care in many hip fracture pathways despite the 2011 guidelines from the Association of Anaesthetists of Great Britain and Ireland (AAGBI) which recommend that such screening be performed only if clinically indicated. This study aims to evaluate the use of pre-operative coagulation screening and explore its financial impact. MethodsProspective data was collected in accordance with the “Standardised Audit of Hip Fractures in Europe” (SAHFE) protocol. All patients admitted to our hospital with hip fractures during a 12-month period from November 2011 to November 2012 were analysed. Data including coagulation results and the use of vitamin K or blood products were collected retrospectively from the hospital computer system. Patient subgroup analysis was performed for intraoperative blood loss, post-operative blood units transfused, haematoma formation and gastrointestinal haemorrhage. Results814 hip fractures were analysed. 91.4% (n=744) had coagulation tests performed and 22.0% (n=164) had an abnormal result. Of these, 55 patients were taking warfarin leaving 109 patients who had abnormal results and were not taking warfarin. When this group (n=109) was compared to those who had normal test results (n=580) and to all other patients (n=705) there was no difference in intraoperative blood loss (p=0.79, 0.78), postoperative transfusion (p=0.38, 0.30), postoperative haematoma formation (p=0.79, 1.00), or gastrointestinal haemorrhage (p=0.45, 1.00), respectively. In those who were not taking warfarin, but had abnormal results, none had treatment to reverse their coagulopathy with either vitamin K or blood products. By omitting pre-operative coagulation tests in patients who are not taking warfarin, we estimate a financial saving of between £66,500 and £432,250 per annum. ConclusionsThis study supports the hypothesis that routine pre-operative coagulation screening is unnecessary in hip fracture patients unless they take warfarin or have a known coagulopathy. Moreover, its omission represents significant cost-saving potential.

The Prevalence of Abnormal Coagulation Tests in Patients Undergoing Abdominal Based Free Flap Surgery for Breast Reconstruction - an Audit Based Practice Recommendation

Introduction: In recent decades, abdominal based free tissue transfer has become increasingly popular for breast reconstruction, and technical advancements in this type of surgery have significantly reduced flap failure rate. However, undiagnosed hematological disorders including hypercoagulopathies and hemophilia can result in complications such as anastomotic thrombosis, excessive bleeding, and hematoma formation. These complications may lead to significant consequences such as re-operation or flap failure. The aim of this audit was to determine whether coagulation screen blood tests were routinely performed prior to surgery and to investigate the prevalence of abnormal findings in these tests.

Performance of coagulation tests in patients on therapeutic doses of rivaroxaban

Knowledge of anticoagulation status during rivaroxaban therapy is desirable in certain clinical situations. It was the study objective to determine coagulation tests most useful for assessing rivaroxaban's anticoagulant effect. Peak and trough blood samples from 29 patients taking rivaroxaban 20 mg daily were collected. Mass spectrometry and various coagulation assays were performed. "On-therapy range" was defined as the rivaroxaban concentrations determined by LC-MS/MS. A "misprediction percentage" was calculated based on how often results of each coagulation assay were in the normal reference range, while the rivaroxaban concentration was in the "on-therapy" range. The on-therapy range was 8.9-660 ng/ml. The misprediction percentages for prothrombin time (PT) and activated partial thromboplastin time (aPTT), using multiple reagents and coagulometers, ranged from 10%-52% and 31%-59%, respectively. PT, aPTT and activated clotting time (ACT) were insensitive to trough rivaroxaban: 59%, 62%, and 80% of samples had a normal result, respectively. Over 95% of PT and ACT values were elevated at peak. Four different rivaroxaban calibrated anti-Xa assays had R² values >0.98, demonstrating strong correlations with rivaroxaban drug levels. In conclusion, PT, aPTT and ACT are often normal in patients on therapeutic doses of rivaroxaban. However, PT and ACT may have clinical utility at higher drug plasma levels. Rivaroxaban calibrated anti-factor Xa assays can accurately identify low and high on-therapy rivaroxaban drug levels and, therefore, have superior utility in all clinical situations where assessment of anticoagulation status may be beneficial.

Early Detection of Coagulation Abnormalities in Patients at Nutritional Risk: The Novel Role of Thromboelastography

It is believed that malnutrition is common among hospitalized patients and associated with increased risk of morbidity and mortality. It is unclear if it is more likely to cause coagulation disorders in patients with malnutrition. We, therefore, investigate the feasibility of using thromboelastography (TEG) in early detection of coagulation abnormalities in patients at nutritional risk. Fifty successive adult patients with gastrointestinal disease were prospectively divided into one of two groups according to nutritional risk score (less than 3 and 3 or greater). Blood samples were collected at admission for analysis of standard biochemical parameters, routine coagulation tests, and TEG parameters. A total of 62 per cent of patients (n = 31) were at nutritional risk. Serum concentrations of prealbumin, transferrin, total protein, low-density lipoprotein, high-density lipoprotein, and cholesterol were much lower in the nutritional risk group than in the no-risk group (P ≤ 0.05). There was no significant difference in routine coagulation tests, whereas most of the TEG parameters showed significant differences between the two groups. The overall coagulation function was worse in patients at nutritional risk than in patients with good nutritional status (P ≤ 0.01). TEG appears to be more sensitive for the detection of coagulation abnormalities compared with routine coagulation tests in patients at nutritional risk. The phenomenon described in this article should be useful in further studies of patients with malnutrition.

Preoperative Thrombocytopenia and Postoperative Outcomes after Noncardiac Surgery

Most studies examining the prognostic value of preoperative coagulation testing are too small to examine the predictive value of routine preoperative coagulation testing in patients having noncardiac surgery. Using data from the American College of Surgeons National Surgical Quality Improvement database, the authors performed a retrospective observational study on 316,644 patients having noncardiac surgery who did not have clinical indications for preoperative coagulation testing. The authors used multivariable logistic regression analysis to explore the association between platelet count abnormalities and red cell transfusion, mortality, and major complications. Thrombocytopenia or thrombocytosis occurred in 1 in 14 patients without clinical indications for preoperative platelet testing. Patients with mild thrombocytopenia (101,000-150,000 µl), moderate-to-severe thrombocytopenia (<100,000 µl), and thrombocytosis (≥450,000 µl) were significantly more likely to be transfused (7.3%, 11.8%, 8.9%, 3.1%) and had significantly higher 30-day mortality rates (1.5%, 2.6%, 0.9%, 0.5%) compared with patients with a normal platelet count. In the multivariable analyses, mild thrombocytopenia (adjusted odds ratio [AOR], 1.28; 95% CI, 1.18-1.39) and moderate-to-severe thrombocytopenia (AOR, 1.76; 95% CI, 1.49-2.08), and thrombocytosis (AOR, 1.44; 95% CI, 1.30-1.60) were associated with increased risk of blood transfusion. Mild thrombocytopenia (AOR, 1.31; 95% CI, 1.11-1.56) and moderate-to-severe thrombocytopenia (AOR, 1.93; 95% CI, 1.43-2.61) were also associated with increased risk of 30-day mortality, whereas thrombocytosis was not (AOR, 0.94; 95% CI, 0.72-1.22). Platelet count abnormalities found in the course of routine preoperative screening are associated with a higher risk of blood transfusion and death.

Performance of coagulation tests in patients on therapeutic doses of dabigatran: a cross‐sectional pharmacodynamic study based on peak and trough plasma levels

Knowledge of anticoagulation status during dabigatran therapy may be desirable in certain clinical situations. To determine the coagulation tests that are most useful for assessing dabigatran's anticoagulant effect. Peak and trough blood samples from 35 patients taking dabigatran 150mg twice daily, and one sample each from 30 non-anticoagulated individuals, were collected. Mass spectrometry and various coagulation assays were performed. 'Therapeutic range' was defined as the range of plasma dabigatran concentrations determined by mass spectrometry between the 2.5th and 97.5th percentiles of all values. The therapeutic range was 27-411ngmL(-1) . The prothrombin time (PT) and activated partial thromboplastin time (APTT), determined with multiple reagents, and activated clotting time (ACT) were insensitive to therapeutic dabigatran: 29%, 18% and 40% of samples had a normal PT, APTT, and ACT, respectively. However, normal PT, ACT and APTT ruled out dabigatran levels above the 75th percentile. The thrombin clotting time (TCT) correlated well and linearly with dabigatran levels below the 50th percentile, but was unmeasurable above it. The dilute thrombin time, ecarin clotting time and ecarin chromogenic assay showed linear correlations with dabigatran levels over a broad range, and identified therapeutic and supratherapeutic levels. The prothrombin time, APTT and ACT are often normal in spite of therapeutic dabigatran plasma levels. The TCT is useful for detecting minimal dabigatran levels. The dilute thrombin time and chromogenic and clotting ecarin assays accurately identify therapeutic and supratherapeutic dabigatran levels. This trial is registered at www.clinicaltrials.gov (#NCT01588327).

Clinical utility of viscoelastic tests of coagulation in patients with liver disease

The prothrombin time (PT) and international normalised ratio (INR) are used in scoring systems (Child-Pugh, MELD, UKELD) in chronic liver disease and as a prognostic tool and for dynamic monitoring of hepatic function in acute liver disease. These tests are known to be poor predictors of bleeding risk in liver disease; however, they continue to influence clinical management decisions. Recent work on coagulation in liver disease, in particular thrombin generation studies, has led to a paradigm shift in our understanding and it is now recognised that haemostasis is relatively well preserved. Whole blood global viscoelastic tests (TEG(®) /ROTEM(®) ) produce a composite dynamic picture of the entire coagulation process and have the potential to provide more clinically relevant information in patients with liver disease. We performed a systematic review of all relevant studies that have used viscoelastic tests (VET) of coagulation in patients with liver disease. Although many studies are observational and small in size, it is clear that VET provide additional information that is in keeping with the new concepts of how coagulation is altered in these patients. This review provides the basis for large scale, prospective outcome studies to establish the clinical value of these tests.

Abstract 416: Dysregulated Coagulation from Coexisting Hypofibrinogenemia and Elevated Factor VIII

Introduction and Objective— Although abnormal clotting factors are typically identified and examined in isolation, dysregulated coagulation can result from multiple independent, co-existing abnormalities. Herein, we probed the complexity of dysregulated coagulation in humans by characterizing pathophysiologic mechanisms in a patient with both bleeding and thrombosis. Methods and Results— A patient with a normal activated partial thromboplastin time (29.6 sec), prolonged thrombin and reptilase times (22.6 and 21.3 sec, respectively), and decreased functional and antigenic fibrinogen levels (162 and 148 mg/dL, respectively) was initially diagnosed with hypodysfibrinogenemia. This diagnosis was supported by DNA analysis revealing a previously unreported FGB mutation (c.656A&gt;G) predicting a novel Q189R mutation in the mature ββ chain that was present in the heterozygote state. Interestingly, however, turbidity analysis showed purified fibrinogen polymerization 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. Of note, the patient’s peak plasma thrombin generation was significantly higher than normal (267±20 versus 183±16 nM, respectively, p&lt;0.05), attributable to an elevated level of factor VIII (163-225%). Spiking normal plasma with factor VIII to 225% (final) produced a thrombin generation peak that was indistinguishable from the patient. In a carotid artery injury model, hypofibrinogenemic mice (Fgn+/-) infused with factor VIII demonstrated significantly shorter vessel occlusion times than saline-infused Fgn+/- mice (11.8±5.8 versus 20.9±14.7 minutes, respectively, p&lt;0.05). Conclusions— These data associate the patient’s complex bleeding and thrombotic presentations with co-existing hypofibrinogenemia plus elevated FVIII, and indicate hypofibrinogenemia does not mitigate the prothrombotic effects of plasma hypercoagulability. Together, these findings illustrate the challenges of diagnosing complex coagulopathies and underscore the importance of global coagulation testing in patients with compound presentations.

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.

Isolated Prolonged Prothrombin Time Correlates with Serum Immunoglobulin Levels in Patients with Multiple Myeloma

Abstract 1225▪▪This icon denotes a clinically relevant abstract Background:Secondary hemostatic defects resulting in bleeding diathesis occur in a subset of patients with plasma cell neoplasms due to a variety of mechanisms. Abnormal screening coagulation tests are frequently observed in asymptomatic patients with multiple myeloma and other plasma cell neoplasms. However, whether these coagulation abnormalities correlate with changes in serum proteins, diagnosis, or other disease parameters has not been systematically evaluated. Study Design:The objective of this study was to determine the prevalence of abnormal screening coagulation tests in patients with different plasma cell neoplasms and correlate clotting times with clinical history and diagnostic parameters. Methods:The medical records of 292 consecutive patients referred to the Myeloma Institute for Research and Therapy at UAMS from January 2010 to October 2010 were reviewed. Nineteen patients were excluded because they lacked screening coagulation tests or did not fulfill WHO diagnostic criteria for plasma cell neoplasm. Prothrombin time (PT), activated partial thromboplastin time (APTT), and fibrinogen activity were determined using mechanical detection. Abnormal APTT was defined as clotting times outside the normal range (23–36.9 sec). Prolonged PT was defined as ≥15.0 seconds (normal range: 11.5–14.7 sec) or INR > 1.2. Patients with prolonged PT or APTT due to warfarin therapy, liver disease or disseminated intravascular coagulation were also excluded. Results:A total of 79 patients had abnormal screening coagulation tests. An isolated prolonged PT was found in 62 patients (25%) and 10 patients had prolonged PT and APTT (3.5%). An isolated prolonged APTT was present in 2 patients (<1%) and decreased APTT seen in 5 patients (2%). According to the clinical notes, none of the patients had significant bleeding.Patients with isolated prolonged PT (62 total) and patients with normal screening tests (173 total) were compared with respect to age, fibrinogen, serum immunoglobulin level determined by protein electrophoresis, diagnosis, immunoglobulin isotype, and history of previous chemotherapy. There was no difference in age between patients with prolonged PT and those with normal PT (Table 1), previous chemotherapy or immunoglobulin isotype. Fibrinogen was significantly decreased in patients with prolonged PT (Table 1); however, there was no correlation between plasma fibrinogen and PT (p=0.1321). In contrast, serum immunoglobulin levels were significantly greater in patients with a prolonged PT (Table 1) and were positively correlated with PT (Figure 1).Table 1Patient CharacteristicsAll patients (mean ± SEM)PT < 15 sec (mean ± SEM)PT ≥ 15 sec (mean ± SEM)Age (yr)61.4 ± 0.71860.9 ± 0.83262.7 ± 1.415NSFibrinogen (mg/dL)414 ± 7.61427 ± 8.43377 ± 15.84p=0.0057Serum Immunoglobulin (g/dL)1.63 ± 0.1191.11 ± 0.0973.10 ± 0.287p<0.0001Values from patients with PT<15 sec were compared with those with PT≥15 sec using a Mann-Whitney (two-tailed) t-test. [Display omitted] As shown in Table 2, prolonged PT was more frequently observed in patients with multiple myeloma while patients with MGUS were less likely to have prolonged PT. No differences were observed with other plasma cell neoplasms; however, the numbers of patients in these diagnostic groups was small.Table 2:Patient DiagnosisDiagnosisAll PatientsPT <15 secPT ≥ 15 secORMultiple Myeloma (MM)157105523.37 (p=0.0009)MM, Non or Hyposecretory660NSMM with Plasmacytoma440NSSmoldering Myeloma21165NSMGUS343040.33 (p=0.037)Plasmacytoma11101NSAmyloid220NSTotal23517362Incidence of elevated PT in patients with indicated disease was determined by Fisher's exact test. Odds-Ratio (OR) was calculated using GraphPad Prism. Conclusion:An isolated prolonged PT (≥15 sec) was the most common abnormal coagulation test in our cohort. An association between disease severity and prolonged PT is suggested by our finding that patients with multiple myeloma were more likely to have prolonged PT than were patients with other plasma cell neoplasms. Of the factors examined, only serum immunoglobulin levels correlated with PT and were significantly elevated in patients with isolated prolonged PT. Disclosures:No relevant conflicts of interest to declare.

Correlation of early rotation thromboelastography parameters with conventional coagulation tests in patients undergoing liver transplantation

Correlation of early rotation thromboelastography parameters with conventional coagulation tests in patients undergoing liver transplantation

Prevalencia de alteración en las pruebas de coagulación en pacientes sometidos a biopsia transrectal de próstata

Purpose To determine the prevalence of abnormal coagulation tests in patients who undergo transrectal prostate biopsy. Material and methods A cross-sectional study was performed at Hospital Universitario del Valle (HUV) between 1 June and 31 December 2008. Variables collected included age, PSA value, PT (prothrombin time), PTT (partial thromboplastin time) and INR (international normalized ratio) values and the presence of abnormalities in each of the haematological variables. There are no real normal or maximum acceptable values in clinical practice; however, the values described by some authors and different clinical practice protocols serve as a guide. Results The average age was 70 years, the median PSA was 28, the partial thromboplastin time was altered in 2.3% of patients, and INR was abnormal in 3.4% of patients (cut-off point 1.5). There were no changes in PT or INR values (cut-off point 2.0). Conclusions The prevalence of abnormal coagulation tests is low even when there are no clear cut-off points in worldwide literature that would determine abnormality.

The Prevalence of Abnormal Coagulation Parameters in Patients with Newly Diagnosed Primary Systemic Amyloidosis and Its Impact on Outcome

Background: Primary systemic amyloidosis (AL) is an incurable plasma cell disorder associated with varying degree of organ infiltration with light chain derived amyloid protein and consequent organ dysfunction. Various acquired coagulopathies, predominantly Factor X (FX) deficiency have been previously described in AL. The factor deficiencies are thought to be due to the direct binding of blood coagulation proteins to amyloid fibrils. Little is known regarding the prognostic significance of abnormal coagulation parameters in AL patients (pts).Methods: After Institutional Review Board approval, we performed a retrospective review of the medical records of 625 consecutive pts who had presented within 3 months of a diagnosis of AL to be evaluated at Mayo Clinic from June 2001 to June 2006. 540 pts had coagulation studies performed within 2 months of presentation. 51 of those pts were on oral anticoagulation and were excluded from the analysis.Results: Of the 489 pts included in the analysis, the median age was 62 years and 61% were male. The median overall survival (OS) of the entire cohort was 26.8 months. Table 1 lists the prevalence of abnormal coagulation tests in the remaining 489 patients. Prothrombin time (PT) was available in the majority of pts. 61 pts (12.6%) had elevated PT, and 63 pts (20.4%) had a decreased FX. 37 of the 61 pts with elevated PT had available FX levels, of which 31 (84%) of those had a decreased FX, suggesting that the cause of elevated PT was mostly due to a low FX. Indicators of hepatic involvement such as alkaline phosphatase and bilirubin levels were higher among the patients with prolonged PT and low FX. An elevated PT (more than 12.4 seconds) was strongly predictive of an adverse outcome, with a median OS of 8.7 months compared to a median OS of 29 months (p<0.0001) in pts with normal PT (Figure 1). Similarly, pts with decreased FX (less than 60% activity), was associated with significantly worse outcomes with a median OS of 14.9 months versus a median OS of 33 months (p<0.0001) in pts with normal FX (Figure 2). In a Cox proportional hazards model containing cardiac troponin (cTnT), NT-Pro BNP, serum alkaline phosphatase, and free light chain difference (involved minus uninvolved), prolonged PT or FX deficiency were independently prognostic for overall survival.Conclusion: Abnormalities of PT and FX are seen in a sizable proportion of pts with newly diagnosed AL. An elevated PT and or FX deficiency appear to adversely affect the outcome of these patients. It is likely that the elevated PT in these patients relate to FX deficiency in the majority which in turn may reflect the amyloid ‘burden’. The effect of other organ involvement like the hepatic involvement may also have an impact on FX and PT.Table 1. Prevalence of abnormal coagulation testing in patients with newly diagnosed primary systemic amyloidosis.Coagulation studyN (Test results available)N of abnormal results(%)Elevated prothrombin time4866112.6Elevated activated partial thromboplastin time3124815.4Elevated thrombin time3158426.7Elevated fibrinogen14011884.3Decreased Factor II activity622641.9Decreased Factor V activity63914.3Decreased Factor VII activity631727Decreased Factor X activity3096320.4Elevated D-dimer1307255.4 [Display omitted] [Display omitted]

Perioperative blood conservation strategies: weighing the medical evidence — II

To the Editor: We read, with interest, the recent editorial written by Drs. Karkouti and McCluskey.1 The crux of their editorial is that cardiac anesthesiologists should discontinue most blood conservation methods to avoid transfusions in heart surgery patients, until such methods have been proven safe and efficacious. However, the editorial leaves a number of unanswered questions; most importantly, is receiving blood, or blood component therapy, harmful? The authors suggest a causal relationship between the volume of transfusion and mortality. Work in this area has been based upon retrospective, propensity scored, database analysis which describes an association between transfusion and mortality from small to large volume transfusion.2–4 Possibly the nature of the surgical insult, with a requirement for large volume transfusion, is the major determinant for excess mortality, not the consequent transfusion. The findings of well-controlled trials, which examine simple methods to reduce transfusion requirements, can potentially be dismissed, arguing that they are not powered adequately to detect differences in mortality. However, it should be recognized that these studies were frequently not intended to evaluate mortality. There is enormous variation in transfusion practice across centres performing the same type of cardiac operations.5 Many studies have evaluated methods that might reduce this variation in practice. Simple organizational changes and audit of practice may be just as effective in reducing transfusion rates as using mechanical or pharmacological methods. We have a safe blood supply; but this editorial largely ignores the wider issues around an increasingly scarce and expensive product. In addition, preventing low volume transfusions may be important to functional outcome after cardiac surgery.6 In the void left after the closure of the Blood conservation using antifibrinolytics: a randomized trial in a cardiac surgery population study, have Karkouti and McCluskey stopped using tranexamic acid in patients not involved in randomized clinical trials? Are they suggesting that units should stop using standard tests of coagulation in patients, as the value of these tests have not been validated in hemodiluted post-cardiopulmonary bypass coagulopathic patients? The authors have produced a stimulating editorial. To do no harm, we must first correct the balance between transfusion and conservation approaches. This will require primary and database research into transfusion of blood, use of component therapy, and mechanical and pharmacological methods to reduce transfusion. At a time when aprotinin has been removed from our armamentarium, abandonment of a range of methods of transfusion avoidance may not be timely.

Perioperative blood conservation strategies: weighing the medical evidence — I

To the Editor: We read, with interest, the recent editorial written by Drs. Karkouti and McCluskey.1 The crux of their editorial is that cardiac anesthesiologists should discontinue most blood conservation methods to avoid transfusions in heart surgery patients, until such methods have been proven safe and efficacious. However, the editorial leaves a number of unanswered questions; most importantly, is receiving blood, or blood component therapy, harmful? The authors suggest a causal relationship between the volume of transfusion and mortality. Work in this area has been based upon retrospective, propensity scored, database analysis which describes an association between transfusion and mortality from small to large volume transfusion.2–4 Possibly the nature of the surgical insult, with a requirement for large volume transfusion, is the major determinant for excess mortality, not the consequent transfusion. The findings of well-controlled trials, which examine simple methods to reduce transfusion requirements, can potentially be dismissed, arguing that they are not powered adequately to detect differences in mortality. However, it should be recognized that these studies were frequently not intended to evaluate mortality. There is enormous variation in transfusion practice across centres performing the same type of cardiac operations.5 Many studies have evaluated methods that might reduce this variation in practice. Simple organizational changes and audit of practice may be just as effective in reducing transfusion rates as using mechanical or pharmacological methods. We have a safe blood supply; but this editorial largely ignores the wider issues around an increasingly scarce and expensive product. In addition, preventing low volume transfusions may be important to functional outcome after cardiac surgery.6 In the void left after the closure of the Blood conservation using antifibrinolytics: a randomized trial in a cardiac surgery population study, have Karkouti and McCluskey stopped using tranexamic acid in patients not involved in randomized clinical trials? Are they suggesting that units should stop using standard tests of coagulation in patients, as the value of these tests have not been validated in hemodiluted post-cardiopulmonary bypass coagulopathic patients? The authors have produced a stimulating editorial. To do no harm, we must first correct the balance between transfusion and conservation approaches. This will require primary and database research into transfusion of blood, use of component therapy, and mechanical and pharmacological methods to reduce transfusion. At a time when aprotinin has been removed from our armamentarium, abandonment of a range of methods of transfusion avoidance may not be timely.

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