Déficit de factor V grave / Severe factor V deficiency

Se presenta un caso de factor V severo, deficiencia (<1%) asociada con múltiples episodios de sangrado en diferentes zonas del cuerpo. El curso clínico ha sido complicado aún más por el desarrollo de reacciones transfusionales, tras tratamiento con plasma fresco congelado. Sería interesante realizar investigaciones para poder disponer de factor V purificado (AU)

We present a case of severe factor V, deficiency (<1%) associated with multiple episodes of bleeding in different areas of the body. The clinical course has been further complicated by the development of transfusion reactions following treatment with Fresh Frozen Plasma. It would be interesting to carry out investigations in order to have purified factor V (AU)

Lupus anticoagulant - hypoprothrombinemia syndrome: a rare cause of intracranial bleeding.

: We report a 14-year-old girl who presented with subdural hematoma and a deranged coagulation profile suggestive of an inhibitor. Investigations revealed prothrombin deficiency along with positivity for antiphospholipid antibodies, which improved with steroid therapy. Bleeding diathesis in children and adolescents commonly results from thrombocytopenia, platelet function disorders, or coagulation factor deficiency; whereas bleeding because of coagulation factor inhibitors are extremely rare in this age group. This case also highlights the uncommon presentation of antiphospholipid antibody syndrome, as they often present with thrombosis or pregnancy complications rather than bleeding.

On the importance of albumin binding for the flux of 7α-hydroxy-3-oxo-4-cholestenoic acid in the brain.

We confirmed previous findings by a Japanese group that there is an accumulation of 7α-hydroxy-3-oxo-4-cholestenoic acid (7-Hoca) in human subdural hematomas. The accumulation correlated with the time from the bleeding to the sample collection. We present evidence that these accumulations are likely to be caused by the strong affinity of 7-Hoca to albumin and the marked difference between plasma and brain with respect to levels of albumin. In the circulation, 80-90% of 7-Hoca is bound to albumin with a ratio between the steroid acid and albumin of ∼1.4 ng/mg. In cerebrospinal fluid (CSF), the ratio between 7-Hoca and albumin is ∼30 ng/mg. When albumin or hemolyzed blood in a dialysis bag was exposed to CSF, there was a flux of 7-Hoca from CSF to the albumin. We suggest that the major explanation for accumulation of 7-Hoca in subdural hematoma is a flux from the brain into the hematoma due to the high affinity to albumin and the high capacity of 7-Hoca to pass biomembranes. We discuss the possibility that the markedly different ratios between 7-Hoca and albumin in circulation and brain can explain the flux of 7-Hoca from the brain into circulation against a concentration gradient.

Fatal hemorrhage due to a spontaneous factor V inhibitor with lupus anticoagulant properties.

: Factor V inhibitors are rare and have varied clinical presentations. We report on a 76-year-old female admitted to the hospital for pneumonia and treated with multiple antibiotics. Her baseline prothrombin time was 15.6 s and the activated partial thromboplastin time was 35 s. On admission day 10, she developed arm weakness and brain imaging showed a subdural hematoma. The prothrombin time was now 59.1 s with an activated partial thromboplastin time of more than 160 s and a normal thrombin time. A mixing study did not correct the clotting times and coagulation factor assays showed a nonspecific inhibition pattern. Only factor V activity remained low with serial dilutions, however, and a 70 Bethesda Unit inhibitor was identified. Aggressive supportive care was initiated but the patient succumbed to the effects of the intracranial hemorrhage. Factor V inhibitors may display lupus anticoagulant properties and may cause catastrophic bleeding. Our case illustrates that these inhibitors can arise quickly and supports an association with antibiotics.

Bilateral subdural hematomas, an unusual vaso-occlusive event and prolonged prothrombin time in a 58-year-old victim of an armed robbery.

Factor VII deficiency is one of the most common of rare bleeding disorders(1). This autosomal recessive disorder has a prevalence of 1:500,000 with geographic variations. Clinical manifestations vary from asymptomatic to severe mucocutaneous bleeding. According to the International Registry of Factor VII Deficiency (IRF7) epistaxis is the most common clinical manifestation. Gastrointestinal and central nervous system(CNS) bleeding are rare presentations.(2-4) We present here the case of a patient with life-threatening CNS bleeding who was found at the age of 58 years to have congenital factor VII deficiency.

My paper 20 years later: cerebral venous oxygen saturation studied with bilateral samples in the internal jugular veins.

INTRODUCTION: Jugular oxygen saturation monitoring was introduced in neurointensive care after severe traumatic brain injury (TBI) to explore the adequacy of brain perfusion and guide therapeutic interventions. The brain was considered homogeneous, and oxygen saturation was taken as representative of the whole organ. We investigated whether venous outflow from the brain was homogeneous by measuring oxygen saturation simultaneously from the two jugular veins. METHODS: In 32 comatose TBI patients both internal jugular veins (IJs) were simultaneously explored using intermittent samples; hemoglobin saturation was also recorded continuously by fiber-optic catheters in five patients. In five cases long catheters were inserted bilaterally upstream, up to the sigmoid sinuses. MAIN FINDINGS: On average, measurements from the two sides were in agreement (mean and standard deviation of the differences between the saturation of the two IJs were respectively 5.32 and 5.15). However, 15 patients showed differences of more than 15 % in hemoglobin saturation at some point; three others showed differences larger than 10 %. No relationship was found between the computed tomographic scan data and the hemoglobin saturation pattern. DISCUSSION/CONCLUSION: Several groups have confirmed differences between oxygen saturation in the two jugular veins. After years of enthusiasm, interest for jugular saturation has decreased and more modern methods, such as tissue oxygenation monitoring, are now available. Jugular saturation monitoring has low sensitivity, with the risk of missing low saturation, but high specificity; moreover it is cheap, when used with intermittent sampling. Monitoring the adequacy of brain perfusion after severe TBI is essential. However the choice of a specific monitor depends on local resources and expertise.

Analysis of S100 calcium binding protein B serum levels in different types of traumatic intracranial lesions.

The objective of this study was to determine whether the type of intracranial traumatic lesions, the number of simultaneous traumatic lesions, and the occurrence of skull and facial bone fractures have an influence on S100 calcium binding protein B (S100B) serum levels. Patients with blunt traumatic brain injury were prospectively enrolled into this cohort study over a period of 13 months. Venous blood samples were obtained prior to emergency cranial CT scan in all patients within 3 h after injury. The patients were then assigned into six groups: 1) concussion, 2) epidural hematoma, 3) subdural hematoma, 4) subarachnoid hemorrhage, 5) brain contusions, and 6) brain edema. The study included 1696 head trauma patients with a mean age of 57.7 ± 25.3 years, and 126 patients (8%) had 182 traumatic lesions on CT. Significant differences in S100B serum levels were found between cerebral edema and the other four bleeding groups: epidural p = 0.0002, subdural p < 0.0001, subarachnoid p = 0.0001, brain contusions p = 0.0003, and concussion p < 0.0001. Significant differences in S100B values between patients with one or two intracranial lesions (p = 0.014) or with three (p < 0.0001) simultaneous intracranial lesions were found. In patients with intracranial traumatic lesions, skull fractures, as well as skull and facial bone fractures occurring together, were identified as significant additional factors for the increase in serum S100B levels (p < 0.0001). Older age was also associated with elevated S100B serum levels (p < 0.0001). Our data show that peak S100B serum levels were found in patients with cerebral edema and brain contusions.

The influence of coagulopathy on outcome after traumatic subdural hematoma: a retrospective single-center analysis of 319 patients.

The aim of this study was to identify the effects of coagulopathy on the outcome of patients with traumatic subdural hematoma (SDH). Based on a retrospective study, the records of all patients admitted between 2001 and 2007 to a large emergency hospital with acute SDH resulting from traumatic brain injury (TBI) were analyzed. An initial Glasgow coma score (GCS), clinical state, and Glasgow outcome score (GOS) were recorded for all patients. All computer assisted tomography and MRI scans obtained from patients were saved on an electronic storage device and were reviewed by a neurosurgeon and a neuroradiologist. The coagulation parameters were analyzed for all patients. Coagulopathy was defined as international normalized ratio more than 1.2 or partial thromboplastin time more than 37 s. One hundred and five women and 214 men aged between 1 and 100 years (mean 59 years) were included in the study. Patients with coagulopathy had a significantly worse outcome. Almost twice as many patients died in the coagulopathy group (mean GOS 3.10 ±â€Š1.46) than in the group without coagulopathy (mean GOS 2.16 ±â€Š1.45), (P < 0.001). In-hospital mortality is twice as frequent in patients with coagulopathy with traumatic SDH compared with noncoagulopathic patients, even if the initial severity of the TBI does not differ.

Dabigatran-associated subdural hemorrhage: using thromboelastography (TEG(®)) to guide decision-making.

Novel oral anticoagulants present challenges and uncertainties in the management of hemorrhagic emergencies. An 84-year-old man taking dabigatran presented with a subdural hematoma requiring neurosurgical intervention. Routine coagulation assays were prolonged at admission and following administration of Factor VIII Inhibitor Bypassing Activity (FEIBA). Thromboelastography (TEG(®)) was utilized to assess clot dynamics prior to placement of a subdural drain, which was safely inserted despite a prolonged thrombin time (TT). Exclusive reliance on the TT may delay necessary interventions. TEG(®) may be a valuable tool to investigate hemostasis in patients on dabigatran requiring emergent procedures.

Increased number of fetal nucleated red blood cells in the placentas of term or near-term stillborn and neonates correlates with the presence of diffuse intradural hemorrhage in the perinatal period.

Release of nucleated red blood cells (nRBCs) into the peripheral blood occurs in stillbirths/neonates with a probable hypoxic mode of death and antenatal stress. We correlated the number of nRBCs in the placenta with the occurrence of intradural (IDH) and subdural hemorrhage (SDH) and the potential link with fetal hypoxia. Two groups of 22 cases each of nonmacerated term or near-term (≥36 weeks of gestational age) stillborn or newborns dying in the 1st day of life were studied. One group had IDH (with or without SDH) and the other did not have IDH or SDH. In each case, the number of nRBCs was determined in 10 consecutive placental fields at ×40. Data were analyzed with Fisher exact test, receiver operating characteristic (ROC) curve analysis, and logistic regression. There was a significant association between the diffuse IDH and increased number of nRBCs (Fisher exact test P  =  0.0165). An ROC curve analysis showed that the cut-off number of nRBCs with the highest accuracy was 2.15 nRBCs/high-power field, with 79% sensitivity and 67% specificity. The presence of diffuse IDH was associated with SDH (Fisher exact test, P  =  0.002). The absence of hypoxic brain change was associated with the absence of diffuse IDH (odds ratio 0.308; P  =  0.039). We established a significant correlation between the release of nRBCs into the placental circulation and the occurrence of diffuse IDH and between diffuse IDH and the presence of SDH.

[BNP elevation due to a subdural hematoma - misled by a biomarker]. / BNP-Erhöhung bei subduralem Hämatom - durch einen Biomarker in die Irre geführt.

HISTORY AND ADMISSION FINDINGS: A 73-year-old man with a mechanical aortic valve and a history of congestive heart failure was admitted to our hospital with an unspecifically reduced general condition. Physical examination was normal according to age apart from mechanic valve closure tones and a 2/6 sytolic murmur at Erb's point. INVESTIGATIONS: Inflammation markers were elevated (leukocytosis 22 100/µl, CRP 22 mg/dl ), there was mild anemia (hemoglobin 9.7 mg/dl) and digitoxin blood level was increased to 56 µg/l (therapeutic range 10-30 µg/l). Because NT-proBNP was highly elevated, further diagnostics focused on cardiac causes of BNP elevation despite missing clinical symptoms. Transesophageal echocardiography was inconspicuous and blood cultures were negative. Therefore an infection of unknown origin or an emerging endocarditis were presumed. TREATMENT AND COURSE: Pragmatic treatment with antibiotics and diuretics as well as discontinuation of digitoxin led to normalization of leukocytes, CRP and digitoxin levels. But the patient's general condition deteriorated further, NT-proBNP rose to 37731 pg/ml and the patient became disoriented. On thorough questioning the patient's relatives stated that he had fallen 6 weeks previously. Computed tomography then revealed a large chronic subdural hematoma which had caused the NT-proBNP elevation. The patient was operated successful. CONCLUSION: In patients with elevated BNP and atypical symptoms neurological causes should be considered.

Mild elevations of international normalized ratio at hospital Day 1 and risk of expansion in warfarin-associated subdural hematomas.

OBJECT: A primary goal in the treatment of patients with warfarin-associated subdural hematoma (SDH) is reversal of coagulopathy with fresh-frozen plasma. Achieving the traditional target international normalized ratio (INR) of 1.3 is often difficult and may expose patients to risks of volume overload and of thromboembolic complications. This retrospective study evaluates the risk of mild elevations of INR from 1.31 to 1.69 at 24 hours after admission in patients presenting with warfarin-associated SDH. METHODS: Sixty-nine patients with warfarin-associated SDH and 197 patients with non-warfarin-associated SDH treated at a single institution between January 2005 and January 2012 were retrospectively identified. Charts were reviewed for patient age, history of trauma, associated injuries, neurological status at presentation, size and chronicity of SDH, associated midline shift, INR at admission and at hospital Day 1 (HD1), concomitant aspirin or Plavix use, platelet count, and medical comorbidities. Patients were stratified according to use of warfarin and by INR at HD1 (INR 0.8-1.3, 1.31-1.69, 1.7-1.99, and ≥ 2). The groups were evaluated for differences the in rate of radiographic expansion of SDH and in the rate of clinically significant SDH expansion resulting in death, unplanned procedure, and/or readmission. RESULTS: There was no difference in the rate of radiographic versus clinically significant expansion of SDH between patients not on warfarin and those on warfarin (no warfarin: 22.3% vs 20.3%, p = 0.866; warfarin: 10.7% vs 11.6%, p = 0.825), but the rate of medical complications was significantly higher in the warfarin subgroup (13.3% for patients who did not receive warfarin vs 26.1% for those who did; p = 0.023). For warfarin-associated SDH, there was no difference in the rate of radiographic versus clinically significant expansion between patients reversed to HD1 INRs of 0.8-1.3 and 1.31-1.69 (HD1 INR 0.8-1.3: 22.5% vs 20%, p = 1; HD1 INR 1.31-1.69: 15% vs 10%, p = 0.71). CONCLUSIONS: Mild INR elevations of 1.31-1.69 in warfarin-associated SDH are not associated with a markedly increased risk of radiographic or clinically significant expansion of SDH. Larger prospective studies are needed to determine if subtherapeutic INR elevations at HD1 are associated with smaller increases in risk of SDH expansion.

Severe inhibitor-negative acquired factor XIII/13 deficiency with aggressive subdural haemorrhage.

Acquired factor XIII (FXIII) deficiency is a common disease and seldom causes bleeding. However, severe FXIII deficiency may result in life-threatening bleeding. Although the inhibitor against FXIII has recently been focused as the cause of haemorrhagic acquired FXIII deficiency, the pathophysiology of inhibitor-negative cases could also be involved. We report a case of an 85-year-old Japanese man with serious subdural haemorrhage showing a remarkable decreased level of FXIII activity. He also manifested complications of compensated disseminated intravascular coagulation (DIC) with chronic renal failure, abdominal aortic aneurysm (AAA) and right renal carcinoma. Despite the successful evacuation of the haemorrhage, acute subdural haemorrhage subsequently developed that necessitated further craniotomies. Plasma cross-mixing studies and dot blot assay revealed no inhibitors against FXIII. We speculated that the decreased FXIII activity could be mainly due to hyperconsumption by DIC and surgery. Because plasma-derived FXIII concentrates are available to stop bleeding, clinicians should be aware of severe acquired inhibitor-negative FXIII deficiency in cases of unexplained excessive bleeding.

Ability of S100B to predict severity and cranial CT results in children with TBI.

OBJECTIVES: To evaluate the ability of S100B to predict severity of TBI and abnormal cranial CT results for children with TBI. METHODS: This is a secondary analysis of a previously established cohort of consecutive patients presenting to the emergency department with TBI limited to children <19 years of age, who arrived within 6 hours of injury, received a cranial CT scan and consented to blood drawn for S100B. RESULTS: A total of 109 children were included in this cohort. The mean S100B levels were higher in children with moderate/severe TBI as compared to children with mild TBI based GCS score (0.281 µg L(-1), 95%CI = 0.101, 0.461 vs 0.053, 95%CI = 0.010, 0.095). S100B levels were significantly elevated in children following TBI with abnormal cranial CT as compared to children with a normal cranial CT (0.210 µg L(-1), SD = 0.313 vs 0.036 µg L(-1), SD = 0.046, p = 0.03). Area under the curve for S100B was also significant (0.72, 95%CI = 0.58, 0.86) for prediction of abnormal cranial CT for children with TBI. S100B did not predict abnormal cranial CT for children following TBI with a GCS of 15 (AUC = 0.53, 95%CI = 0.36, 0.71). CONCLUSIONS: For children following TBI, S100B appears to predict severity of TBI; however, it may not be clinically useful as an independent screening test to select children with mild TBI who need a cranial CT.

Steady-state pharmacokinetics of intravenous levetiracetam in neurocritical care patients.

STUDY OBJECTIVES: To characterize the steady-state pharmacokinetics of intravenous levetiracetam in neurocritical care patients requiring seizure prophylaxis after a neurologic injury and to determine which dosing regimens achieve serum concentrations within the recommended therapeutic range of 6-20 µg/ml. DESIGN. Prospective, open-label, steady-state pharmacokinetic study. SETTING: Neurocritical care unit in a tertiary care medical center. PATIENTS. Twelve adults (five men, seven women) admitted to the neurocritical care unit who required prophylactic anticonvulsant therapy after subarachnoid hemorrhage, subdural hematoma, or traumatic brain injury. INTERVENTION: Patients received an intravenous infusion of levetiracetam 500 mg over 15 minutes every 12 hours. MEASUREMENTS AND MAIN RESULTS: Serial blood samples were collected from all patients after a minimum of four doses of therapy. Serum levetiracetam concentrations were determined by ultraperformance liquid chromatography with tandem mass spectrometry detection, and pharmacokinetic data were analyzed by compartmental and noncompartmental methods. Monte Carlo simulations were performed for multiple levetiracetam dosing regimens to determine the probability of achieving a target trough concentration of 6 µg/ml or greater, 20 µg/ml or greater, and 6-20 µg/ml. The mean ± SD levetiracetam maximum serum concentration was 28.0 ± 8.0 µg/ml, minimum serum concentration 3.1 ± 1.8 µg/ml, half-life 5.2 ± 1.2 hours, systemic clearance 5.6 ± 1.8 L/hour, and volume of distribution at steady state 36.8 ± 6.3 L. Increasing the doses of levetiracetam increased the probability of achieving a target trough concentration of 6 µg/ml or greater but also increased the probability of achieving trough concentrations greater than 20 µg/ml. Levetiracetam doses of 1000 mg every 8 hours and 1500-2000 mg every 12 hours provided the highest probability of achieving a target trough concentration between 6 and 20 µg/ml. CONCLUSION: Compared with previously published results in healthy volunteers and adults in status epilepticus, levetiracetam systemic clearance was faster and the terminal elimination half-life was shorter in neurocritical care patients. Higher doses or more frequent dosing may be needed to achieve target trough concentrations of 6-20 µg/ml.

Nontraumatic bilateral subdural hematoma caused by antiaggregation therapy: case report and review of the literature.

A 64-year-old female receiving clopidogrel and aspirin antiaggregation therapy after percutaneous coronary intervention for non-STEMI myocardial infarction developed nontraumatic bilateral subdural hematoma with dizziness, vertigo and headache. Craniotomy had to be postponed because of reduced ADP platelet aggregability. Four days after clopidogrel withdrawal and transfusion of 12 platelet concentrate units, ADP aggregation transiently normalized and bilateral trepanation with hematoma evacuation was performed. The procedure was followed by excellent neurologic and clinical recovery; however, decreased platelet aggregability was recorded by postoperative day 12 despite strict clopidogrel and other platelet inhibitor withdrawal. Suspicion of Glanzmann thrombastenia was excluded by flow cytometry. Two weeks after neurosurgery, the right femoral vein thrombosis was detected by color doppler ultrasonography and therapy with fractionated heparin was initiated, followed by warfarin. The risk and incidence of hemorrhagic complications of antiaggregation and anticoagulation therapy are discussed. Caution is warranted on prescribing this potentially harmful therapy to older patients, generally burdened with other chronic comorbidities.

Slippery platelet syndromes in subdural hematoma.

BACKGROUND: This study investigates platelet dysfunction in patients with subdural hematomas (SDH) using platelet function analysis (PFA). METHODS: PFA using the PFA-100 (Dade International Inc., Miami, FL) was performed at admission using the collagen-epinephrine and collagen-ADP assays in 58 SDH patients. Clinical and radiologic information was collected. RESULTS: Normal PFA results were present in 36 patients (62%; PFA collagen:epinephrine assay (s) 118 ave; PFA collagen:adenosine diphosphate assay (s) ave 75) and abnormal platelet function in 22 patients (38%; PFA collagen:epinephrine assay (s) 231 average; PFA collagen:adenosine diphosphate assay (s) 124 average). Compared to patients with normal PFA results, patients with abnormal PFA results were more likely to have hypertension (22 vs. 55%; P = 0.01), take clopidogrel (3 vs. 32%; P = 0.001), and use anti-platelet medications and non-steroidal anti-inflammatory agents (22 vs. 59%; P = 0.004). Measurements of baseline CT for midline shift, maximum thickness, presence of blood/fluid levels in the hematoma, and presence of additional sites of intracranial bleeding did not reveal significant differences based on PFA testing. Platelet dysfunction improved after platelet transfusions (PFA collagen:epinephrine assay: baseline 270 s, CI 61 s; after transfusion 124 s, CI 50 s, P < 0.001). CONCLUSION: Platelet dysfunction was found in 38% of SDH patients. This finding adds to our understanding of the pathophysiology of SDH. Since platelet transfusions are indicated for platelet dysfunction accompanied by major bleeding or need for surgery, these results impact peri-operative management.

[Determination of the age of subdural hematomas from the concentration of hemoglobin].

The photocolorimetric method was employed to measure hemoglobin levels in 46 traumatic subdural hematomas of different age. The data thus obtained were used to construct a logarithmic regression model for the determination of the age of subdural hematomas from the concentration of hemoglobin. The model allows to determine injury time points and intervals at any desired level of confidence probability. The fraction of dispersion of hematoma age values attributable to regression was estimated at 41% which accounts for 74.7% of the maximally possible magnitude. Results of the study can be used in practical work of a forensic-medical experts.