Incipient progressive supranuclear palsy is more common than expected and may comprise clinicopathological subtypes: a forensic autopsy series.

We investigated 998 serial Japanese forensic autopsy cases (0-101 years old, mean age 61.7 ± 21.9), with no case selection, using immunohistochemistry to detect cases with progressive supranuclear palsy (PSP). Twenty-nine cases (mean age 82.3 ± 7.2 years, 11 males, 18 females) fulfilled the National Institute of Neuronal Disorders and Stroke (NINDS)-PSP pathological criteria (2.9% of all cases, 4.6% of cases over 60). All had neuronal and glial inclusions in the basal ganglia and brainstem. However, 13 cases had low tau pathology and were categorized as atypical PSP. In addition to PSP pathology, multiple types of astrocytic inclusions and comorbid proteinopathies, particularly a high prevalence of argyrophilic grain disease, were found. All cases had not been diagnosed with PSP and had preserved daily functioning prior to death. However, 14 (48.3%), 11 (37.9%), and 16 (55.2%) cases showed signs of dementia, depressive state, and gait disturbance, respectively. Sixteen accidental death cases (55.2%), including from falls and getting lost, and 11 suicide cases (37.9%) appear to have a relationship with incipient PSP pathology. Cluster analysis using the distribution and amount of 4-repeat-tau pathology classified the cases into three subgroups: Group 1 (10 cases) had typical PSP pathology and seven cases (70.0%) had dementia as the most frequent symptom; Group 2 (7 cases) had significantly higher frequency of gait disorder (6 cases, 85.7%), and less neocortical tau pathology than Group 1; Group 3 (12 cases) had relatively mild PSP pathology and high argyrophilic grain burdens. Granular-shaped astrocytes were the dominant astrocytic inclusion in all cases. We conclude that in forensic cases incipient PSP occurs with a higher prevalence than expected. If these findings can be extrapolated to other population-based cohorts, PSP may be more common than previously thought.

A Novel Imaging Technique (X-Map) to Identify Acute Ischemic Lesions Using Noncontrast Dual-Energy Computed Tomography.

BACKGROUND: We evaluated whether X-map, a novel imaging technique, can visualize ischemic lesions within 20 hours after the onset in patients with acute ischemic stroke, using noncontrast dual-energy computed tomography (DECT). MATERIALS AND METHODS: Six patients with acute ischemic stroke were included in this study. Noncontrast head DECT scans were acquired with 2 X-ray tubes operated at 80 kV and Sn150 kV between 32 minutes and 20 hours after the onset. Using these DECT scans, the X-map was reconstructed based on 3-material decomposition and compared with a simulated standard (120 kV) computed tomography (CT) and diffusion-weighted imaging (DWI). RESULTS: The X-map showed more sensitivity to identify the lesions as an area of lower attenuation value than a simulated standard CT in all 6 patients. The lesions on the X-map correlated well with those on DWI. In 3 of 6 patients, the X-map detected a transient decrease in the attenuation value in the peri-infarct area within 1 day after the onset. CONCLUSIONS: The X-map is a powerful tool to supplement a simulated standard CT and characterize acute ischemic lesions. However, the X-map cannot replace a simulated standard CT to diagnose acute cerebral infarction.

Study of hemostatic biomarkers in acute ischemic stroke by clinical subtype.

BACKGROUND: We studied the usefulness of hemostatic biomarkers in assessing the pathology of thrombus formation, subtype diagnosis, prognosis in the acute phase of cerebral infarction, and differences between various hemostatic biomarkers. METHODS: Our study included 69 patients with acute cerebral infarction who had been hospitalized within 2 days of stroke onset. Fibrin monomer complex (FMC), soluble fibrin (SF), D-dimer, thrombin-antithrombin III complex, fibrinogen, antithrombin III, and fibrin/fibrinogen degradation products (FDPs) were assayed as hemostatic biomarkers on days 1, 2, 3, and 7 of hospitalization. RESULTS: In the cardioembolic (CE) stroke group, FMC and SF levels were significantly higher on days 1 and 2 of hospitalization, and D-dimer levels were significantly higher on day 1 of hospitalization, compared to the noncardioembolic (non-CE) stroke group. FDP levels were significantly higher at all times in the CE group compared to the non-CE group. Neither the National Institute of Health Stroke Scale (NIHSS) used during hospitalization nor the modified Rankin Scale (mRS) used at discharge found any significant correlations to hemostatic biomarkers, but the NIHSS score during hospitalization was significantly higher in the CE group than in the non-CE group. CONCLUSIONS: Measurements of hemostatic biomarkers, such as FMC, SF, and D-dimer on the early stage of cerebral infarction are useful for distinguishing between CE and non-CE stroke.

Clinicopathological features of acute autonomic and sensory neuropathy.

Acute autonomic and sensory neuropathy is a rare disorder that has been only anecdotally reported. We characterized the clinical, electrophysiological, pathological and prognostic features of 21 patients with acute autonomic and sensory neuropathy. An antecedent event, mostly an upper respiratory tract or gastrointestinal tract infection, was reported in two-thirds of patients. Profound autonomic failure with various degrees of sensory impairment characterized the neuropathic features in all patients. The initial symptoms were those related to autonomic disturbance or superficial sensory impairment in all patients, while deep sensory impairment accompanied by sensory ataxia subsequently appeared in 12 patients. The severity of sensory ataxia tended to become worse as the duration from the onset to the peak phase of neuropathy became longer (P<0.001). The distribution of sensory manifestations included the proximal regions of the limbs, face, scalp and trunk in most patients. It tended to be asymmetrical and segmental, rather than presenting as a symmetric polyneuropathy. Pain of the involved region was a common and serious symptom. In addition to autonomic and sensory symptoms, coughing episodes, psychiatric symptoms, sleep apnoea and aspiration, pneumonia made it difficult to manage the clinical condition. Nerve conduction studies revealed the reduction of sensory nerve action potentials in patients with sensory ataxia, while it was relatively preserved in patients without sensory ataxia. Magnetic resonance imaging of the spinal cord revealed a high-intensity area in the posterior column on T(2)*-weighted gradient echo image in patients with sensory ataxia but not in those without it. Sural nerve biopsy revealed small-fibre predominant axonal loss without evidence of nerve regeneration. In an autopsy case with impairment of both superficial and deep sensations, we observed severe neuronal cell loss in the thoracic sympathetic and dorsal root ganglia, and Auerbach's plexus with well preserved anterior hone cells. Myelinated fibres in the anterior spinal root were preserved, while those in the posterior spinal root and the posterior column of the spinal cord were depleted. Although recovery of sensory impairment was poor, autonomic dysfunction was ameliorated to some degree within several months in most patients. In conclusion, an immune-mediated mechanism may be associated with acute autonomic and sensory neuropathy. Small neuronal cells in the autonomic and sensory ganglia may be affected in the initial phase, and subsequently, large neuronal cells in the sensory ganglia are damaged.

Bilateral subthalamic deep brain stimulation for camptocormia associated with Parkinson's disease.

BACKGROUND: Few multiple case studies of the effects of deep brain stimulation for camptocormia associated with Parkinson's disease have been reported. Although deep brain stimulation was in some cases not effective against camptocormia, it is unclear in which types of patients it was effective in treating camptocormia. OBJECTIVE: We treated 4 Parkinson's disease patients with camptocormia and evaluated their paraspinal muscle status by computed tomography to specify the characteristics of cases of effective treatment. METHODS: The 2 female and 2 male patients in this study were 60-69 years old, with a disease duration from onset to surgery of 7-13 years and a follow-up period of 18-40 months. The electrodes were implanted bilaterally in the subthalamic nuclei. RESULTS: Camptocormia was improved in 3 cases, and was unchanged in the remaining case although other parkinsonian symptoms improved. The computed tomography number of paraspinal muscle in the unimproved patient was much smaller than that in the improved patients. CONCLUSIONS: A relationship may exist between improvement of camptocormia and severity of paraspinal muscle degeneration.

[A case of anti-N-methyl-D-aspartate receptor encephalitis with ovarian teratoma showing excellent recovery with decreasing of anti-N-methyl-D-aspartate receptor antibody].

We report a case of a 17-year-old woman with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, who developed psychiatric symptoms. Pelvic MRI revealed a right ovarian tumor that was suspected of being an ovarian teratoma. On the 27th day after onset, the patient underwent right salpingo-oophorectomy. The histopathological diagnosis was immature ovarian teratoma. Subsequently, 4 double filtration plasmapheresises (DFPP) were performed from day 34 to day 43. Methylprednisolone (1,000 mg/day for 3 days) was started on day 38. With these treatments, consciousness disturbance completely improved, and the patient was discharged on day 50. The serum and cerebrospinal fluid were positive for antibodies against the GluRzeta1 (NR1)-EGFP/GluRepsilon2 (NR2B) heteromer and the GluRzeta1 (NR1) subunit of NMDAR. The patient was hence diagnosed as having anti-NMDAR encephalitis with ovarian teratoma Serial analysis show that the antibodies against NMDAR decreased with improvement of symptoms after the immunotherapy including DFPP treatment.

[Case of branch atheromatous disease presenting capsular warning syndrome].

We report a case of branch atheromatous disease (BAD) presenting capsular warning syndrome, who subsequently showed a complete recovery by the combination therapy as described below. A 54-year-old man with untreated hypertension was admitted to our hospital because of dysarthria and right hemiplegia. The NIHSS on admission was 12 points, but his symptoms soon completely disappeared during examination. After admission administration of aspirin, heparin, atorvastatin and t-PA were started, but stereotyped episodes of dysarthria and the right hemiplegia occurred repeatedly. We added plasma expander, and he thereafter revealed no further ischemic episodes at 22 hours from admission. Over all, he had 15 times of transient ischemic attack with no lasting deficit. The DWI scan obtained 5 hours after the onset demonstrated a high-intensity region in the left putamen to corona radiata. MRA showed no significant abnormalities. He had been diagnosed as having branch atheromatous disease with capsular warning syndrome. The present case suggests that combination therapy including t-PA and plasma expander may be effective to BAD presenting capsular warning syndrome.

[Two cases of cardioembolic stroke with stepwise progression].

We reported two patients of cardioembolic stroke with stepwise progression. Magnetic resonance angiography (MRA) or computed tomographic angiography (CTA) showed narrowing of the middle cerebral artery (MCA) in both patients at the acute phase of onset. Case 1 was classified as "undetermined" based on the TOAST classification although his electrocardiogram revealed atrial fibrillation. Case 2 was classified as "large artery atherosclerosis" with no evidence of cardioembolic source at the acute phase of onset. Follow-up MRA was performed at seventeen days after the onset in case 1 and ten days after the onset in case 2 respectively, which showed complete recanalization of the MCA in each case. The presence of cardioembolic source was also detected in both patients at that time, resulting in the final diagnosis of cardioembolic stroke. Cardioembolic stroke may occasionally present in a stepwise manner suggesting a thrombotic process. When MRA shows stenosis or occlusion of the arteries supplying the cortical areas at the acute phase of onset, it is advisable to examine recanalization of these arteries by follow-up MRA with simultaneous efforts to find out the possible embolic source.

[Case of antiamphiphysin antibody-positive stiff-person syndrome with breast cancer diagnosed by FDG-PET].

We report a case of antiamphiphysin antiboddy-positive stiff-person syndrome associated with breast cancer, which was detected only by FDG-PET. A 46-year-old woman was admitted to our hospital because of painful muscle cramp and stiffness of both legs. Laboratory results were negative for anti-GAD antibody, but highly positive for antiamphiphysin antibody (1: 61,440). She had been diagnosed as having paraneoplastic stiff-person syndrome. However, mammogram, thoracic CT, breast MRI and ultrasonic echography showed no abnormal findings. A whole-body fluorodeoxyglucose (FDG) PET was performed, showing an increased uptake in the left axillary lymph nodes. Then, the left axillary lymph nodes were resected and immunohistochemically diagnosed as breast adenocarcinoma. Treatment of stiff-person syndrome was initiated with corticosteroids followed by chemotherapy against breast cancer, which led to a remarkable improvement of her neurological symptoms. If there is possibility of paraneoplastic syndromes like stiff-person syndrome, FDG-PET is very useful for detecting the occult carcinoma.

[A case of acute disseminated encephalomyelitis concomitant with polyneuropathy associated with anti-lactosylceramide antibody].

We report a case of acute disseminated encephalomyelitis (ADEM) concomitant with polyneuropathy associated with anti-lactosylceramide antibody. A 68-year-old man was admitted to our hospital with ophthalmoparesis, bulbar palsy, tetraplegia after suffering from upper respiratory infection and headache. Subsequently, he developed respiratory failure requiring mechanical ventilation. Fluid-attenuated inversion recovery (FLAIR) MRI showed high intensities in the pons and medulla, and a nerve conduction study revealed motor-dominant axonal polyneuropathy. Although the laboratory tests revealed the presence of anti-lactosylceramide antibody in his serum, he was diagnosed with acute disseminated encephalomyelitis concomitant with polyneuropathy. Whereas the intensive treatment with corticosteroids, plasmapharesis, and high-dose intravenous immunoglobulin (IVIg) brought a moderate improvement, his tetraparesis continued to exist.

[A case of apical hypertrophic cardiomyopathy complicated by cardiogenic cerebral embolism].

We report a patient with apical hypertrophic cardiomyopahty (AHCM) complicated by a cardiogenic cerebral embolism. A 56-year-old man was admitted to our hospital because of a transient ischemic attack. He had been diagnosed as having AHCM at the age of 39 years. The intravenous administration of heparin was immediately started; however, he developed a weakness in his right fingers on the second day. A brain MRI examination showed multiple small infarctions in the cortex of the left frontal and temporal lobes. Transthoracic echocardiography revealed the hypokinetic movement of the myocardium and a thrombus in the apex. We suspected that the hypertrophic apex had become dilated, causing the formation of the thrombus. He then developed a cardiogenic cerebral embolism. The thrombus in the apex disappeared after the continuous administration of heparin intravenously. Here, we emphasize that patients with AHCM in the dilatation phase must receive warfarin therapy to prevent cardiogenic cerebral embolism.

[Clinical features, neuroimaging and prognosis of adult patients with clinically diagnosed acute-onset encephalitis treated at a teaching neurology center in the Toyama area of Japan].

Although acute viral encephalitis (AVE) and acute disseminated encephalomyelitis (ADEM) are etiologically and pathologically distinct, a differential diagnosis between these two disorders is often difficult, especially if the patient exhibits a disturbance in consciousness. To identify useful clinical differences enabling a differential diagnosis to be made at an early stage, we retrospectively analyzed patients who had been admitted to our hospital within the past seven years because of acute-onset encephalitis with a disturbance in consciousness. Eleven adult patients were classified as having AVE, and 8 adult patients were classified as having ADEM within this period. The clinical characteristics of the two groups were then compared. Patients with AVE exhibited a disturbance in consciousness as their first neurological sign, whereas patients with ADEM initially showed focal signs like spastic paralysis, urinary disturbance and ataxia, which were followed by a disturbance in consciousness. ADEM is usually preceded by infection or vaccination, but obtaining a medical history from patients with disturbed consciousness is often difficult Based on the present analysis, the initial manifestation of focal neurological signs may be very useful for distinguishing ADEM from AVE.

[Two cases of myelitis associated with Sjögren syndrome without xerosis: characteristic MRI findings].

We report two cases of myelitis associated with Sjögren syndrome without xerosis. Case 1: A 30-year old woman developed dysesthesia on both upper extremities and weakness of the right arm. A T2-weighted MRI examination showed a high-intensity signal and a swollen lesion between the first and seventh cervical vertebral levels. She was diagnosed as having primary Sjögren syndrome based on the positive finding of a Saxon test, typical salivary gland scintigraphy findings, and an elevated anti-SS-A antibody titer. We suspected that her myelitis was associated with Sjögren syndrome and treated her using steroid therapy. Although her symptoms were alleviated, her myelitis relapsed at the same location after the cessation of steroid therapy. Case 2: A 31-year-old woman developed dysesthesia on her neck and both upper extremities and exhibited tonic spasm. A T2-weighted MRI examination showed a high-intensity signal and a swollen lesion between the first and sixth cervical vertebral levels. She was diagnosed as having primary Sjögren syndrome based on the positive findings of a Rose Bengal test, a Schirmer's test, and a Saxon test as well as typical salivary gland scintigraphy findings and elevated titers of anti-SS-A and anti-SS-B antibodies. We suspected that her myelitis was associated with Sjögren syndrome and treated her using steroid therapy. Her symptoms improved after steroid therapy. Based on these two cases, we concluded that MRI findings for myelitis associated with Sjögren syndrome are characterized by a swollen lesion of more than three vertebral segments in length, and the relapse tends to occur at the same location.

[Cerebral artery lesion in a patient with infective endocarditis: serial MRI and MRA findings of cerebral artery stenosis].

We reported a case of infective endocarditis (IE) complicated with bacterial meningitis and cerebral artery stenosis. A 22-year-old man was admitted to our hospital because of IE. Although benzylpenicillin administration was continued, he abruptly developed consciousness disturbance on the seventh day. His cerebrospinal fluid indicated bacterial meningitis. MRI with gadolinium (Gd) enhancement showed septic embolism in the left parietal lobe and bi-linear enhancement on the right middle cerebral artery (MCA). MRA demonstrated narrowing of the MCA at the same site as the bi-linear Gd enhancement. We considered that these findings show narrowing of the MCA was due to cerebral arteritis. Intravenous administration of ampicillin and cefpirome gradually improved both IE and cerebral artery stenosis. We wish to emphasize that combination of MRI with Gd enhancement and MRA may be useful not only for diagnosis of cerebral artery stenosis but also for evaluation of treatment effect.

Inappropriate secretion of antidiuretic hormone in a patient with chronic inflammatory demyelinating polyneuropathy.

A 54-year-old man suffered from a relapse of chronic inflammatory demyelinating polyneuropathy (CIDP), and developed quadriplegia and somnolence requiring mechanical ventilation for respiratory failure. Serum Na concentration remained at low levels during the clinical course, and a diagnosis of inappropriate secretion of antidiuretic hormone (SIADH) was made. The present case had not only acute aggravation of CIDP with autonomic dysfunction but also intracranial hypertension caused by increased CSF protein (maximum level, 1,315 mg/dl). It seemed likely that injury of the afferent fibers of the baroregulatory pathway or intracranial hypertension might have contributed to SIADH in this patient.

[A case of interval form of carbon monoxide poisoning with a remarkable recovery].

A 69-year-old woman was admitted to our hospital due to an interval form of carbon monoxide (CO) poisoning one month after acute CO poisoning. On admission, she had disorientation, memory disturbance, apathy, masked face, muscle rigidity, bradykinesia and parkisonian gait. An MRI (FLAIR image) revealed high signal intensity lesions in the bilateral globus pallidus and the white matter of the frontal lobe. Hyperbaric oxygen (HBO) therapy at 2 atmospheres for 60 min was given every day, in addition to citicoline, levodopa/DCI and selegiline hydrochloride. Cognitive disturbance and parkinsonism gradually decreased, and abnormal signals in the bilateral globus pallidus and the cerebral white matter were attenuated after the treatment. Neuropsychiatric abnormalities except for a slight gait disturbance disappeared one and a half month after starting the treatment. In addition to HBO therapy, administration of citicoline, lovodopa and selegiline may be useful in the case of the interval form of CO poisoning.

[A case of phenytoin intoxication caused by interaction between phenytoin and capecitabine].

We report a case of phenytoin intoxication caused by an interaction between phenytoin and capecitabine. A 41-year-old woman was started on phenytoin (200 mg p.o. daily) for convulsive attacks due to breast cancer brain metastasis. Three months later, chemotherapy with 2,400 mg/d capecitabine (3 weeks on and 1 week off) and 1,250 mg/d lapatinib was initiated for the treatment of breast cancer. Approximately 10 weeks after starting chemotherapy, the patient began to complain of nausea, vomiting, and unsteadiness, and she was admitted to our hospital. Since her serum phenytoin level was more than 40 µg/mL, she was diagnosed with phenytoin intoxication. Phenytoin is metabolized in the liver, primarily by the CYP2C9 isozyme, which can be competitively inhibited by capecitabine. Thus, we determined that the patient developed phenytoin intoxication due to the interaction between phenytoin and capecitabine. This indicates the importance of considering the potential drug-drug interactions while prescribing anticancer agents and antiepileptic drugs simultaneously.

Neuropsychological Characteristics and Their Association with Higher-Level Functional Capacity in Parkinson's Disease.

BACKGROUND/AIMS: Little is known about the relationship between cognitive functions and higher-level functional capacity (e.g. intellectual activity, social role, and social participation) in Parkinson's disease (PD). The purpose of this study was to clarify neuropsychological characteristics and their association with higher-level functional capacity in PD patients. METHODS: Participants were 31 PD patients and 23 demographically matched healthy controls. Neuropsychological tests were conducted. One year later, a questionnaire survey evaluated higher-level functional capacity in daily living. RESULTS: The PD group scored significantly lower than the control group in all cognitive domains, particularly executive function and processing. Executive function, processing speed, language, and memory were significantly correlated with higher-level functional capacity in PD patients. Stepwise regression showed that only executive function (Trail Making Test-B), together with disease severity (HY stage), predicted the higher-level functional capacity. CONCLUSION: Our findings provide evidence of a relationship between executive function and higher-level functional capacity in patients with PD.

Impact of persistent smoking on long-term outcomes in patients with nonvalvular atrial fibrillation.

BACKGROUND: Although smoking is a risk factor for cardiovascular diseases, little is known about the impact of smoking on long-term outcomes in patients with atrial fibrillation (AF). METHODS: In 426 consecutive patients with nonvalvular AF (mean age, 66 years; 307 men; mean follow-up, 5.8±3.2 years), clinical variables including smoking status, CHADS2, and CHA2DS2-VASc score, incidences of cardiovascular events (stroke, myocardial infarction, or admission for heart failure), bleeding, and mortality were determined. RESULTS: Incidences of intracranial bleeding (0.7% vs 0.1%/year, p<0.01), all-cause mortality (4.9% vs 2.6%/year, p<0.01), and death from stroke (0.8% vs 0.2%/year, p<0.05) were higher in patients with history of smoking than in those without it. Incidence of intracranial bleeding was significantly higher in persistent smokers than in non-persistent smokers (1.2% vs 0.2%/year, p<0.01). History of smoking predicted all-cause mortality [hazard ratio (HR), 2.7; 95% confidence interval (CI), 1.7-4.5; p<0.01] and death from stroke (HR 4.7; 95% CI 1.0-22.3; p<0.05) independent of age, antithrombotic treatment, CHADS2, and CHA2DS2-VASc score. Persistent smoking predicted intracranial bleeding (HR 4.4; 95% CI 1.1-17.6; p<0.05) independent of age and antithrombotic treatment. CONCLUSIONS: Smoking status, independent of age, antithrombotic treatment, and clinical risk factors, predicted long-term adverse outcomes including bleeding events in patients with nonvalvular AF. There might be an obvious impact of persistent smoking on intracranial bleeding.

Aortic spontaneous echocardiographic contrast and hemostatic markers in patients with nonrheumatic atrial fibrillation.

OBJECTIVES: To determine the relationship between spontaneous echocardiographic contrast (SEC) in the descending thoracic aorta and plasma levels of hemostatic markers in patients with nonrheumatic atrial fibrillation (AF). DESIGN AND SETTINGS: A cross-sectional study at a university hospital. PATIENTS AND MEASUREMENTS: In 91 consecutive patients (mean +/- SE age, 70 +/- 1 years; 68 men) with nonrheumatic AF who underwent transesophageal echocardiography, plasma levels of markers for platelet activity (platelet factor 4 [PF4] and beta-thromboglobulin [beta-TG]), thrombotic status (thrombin-antithrombin III complex [TAT]), and fibrinolytic status (D-dimer and plasmin-alpha(2)-plasmin inhibitor complex [PIC]) were determined. RESULTS: Forty-three patients who had aortic SEC (AoSEC) were older (72 years vs 68 years; p < 0.05) and had a higher prevalence of chronic AF (88% vs 52%; p < 0.05) than 48 patients without AoSEC. TAT, PIC, and D-dimer levels were significantly higher in patients with AoSEC than in those without AoSEC, whereas PF4 and beta-TG levels were not different between the two groups. Although the prevalence of cerebral embolism did not differ between the two groups (23% vs 29%), the prevalence of peripheral embolism was higher in patients with AoSEC than in those without AoSEC (10% vs 0%; p < 0.05). Multivariate analysis revealed mitral regurgitation (odds ratio, 7.53; p < 0.02), SEC in the left atrium (odds ratio, 2.14; p < 0.02), and aortic atherosclerosis (odds ratio, 1.87; p < 0.04) emerged as independent predictors of AoSEC. CONCLUSIONS: Patients with nonrheumatic AF who have AoSEC appear to have enhanced coagulation activity but not platelet activity. Intensive anticoagulation treatment might be required for these patients.