Effects of direct oral anticoagulants on thromboelastographic parameters and fibrin clot properties in patients with venous thromboembolism.

Data concerning the impact of direct oral anticoagulants (DOACs) on the thromboelastography (TEG) indices in venousthromboembolism (VTE) patients are limited. The goal of this study was to compare the impact of DOACs on clot properties measured in whole blood using TEG kaolin test and in plasma obtained from real-life VTE patients. We assessed 53 patients, including 20 on rivaroxaban, 20 on apixaban, and 13 on dabigatran. Using the TEG® 5000, coagulation status was evaluated in whole blood samples, while plasma fibrin clot permeability (Ks) and its susceptibility to lysis (CLT) were assessed in citrated plasma. Plasma concentrations of rivaroxaban (99 [48 - 311] ng/ml) and apixaban (85 [40 - 105] ng/ml) were positively associated with Ks and inversely with CLT, while dabigatran concentrations (71 [39 - 98] ng/ml) correlated positively with Ks. Moreover, Ks was associated with clot formation times (R and K), time to maximum clot strength (TMA), coagulation index (CI) reflecting the overall coagulation status, and whole blood clot lysis time (TEG-CLT). Blood clot lysis index (CL30) was associated with plasma CLT in all patients on DOACs, while TMA correlated with CLT only in patients on apixaban. Higher DOAC concentrations were associated with longer retardation of whole blood clot formation and longer time needed to reach maximum level of its strength as well as with more permeable clots. We concluded that plasma fibrin clot properties correlate with corresponding TEG indices suggesting that TEG might be helpful in providing prognostic information about DOAC influence in VTE patients.

Viscoelastic properties of plasma fibrin clots are similar in patients on rivaroxaban and vitamin K antagonists.

Unfavorable fibrin clot features have been observed in patients with venous thromboembolism (VTE). We investigated whether rivaroxaban, a direct factor Xa inhibitor, and vitamin K antagonists (VKAs) can improve plasma clot viscoelastic properties. We studied four age- and sex-matched groups: 25 healthy controls, 15 VTE patients taking rivaroxaban 20 mg/day (blood concentration, 145 (67 - 217) ng/ml), 15 VTE patients taking VKA (INR: 2 - 3), and 15 VTE patients who stopped oral anticoagulant therapy (OAT). Using a hybrid rheometier the storage (G') and loss (G") moduli were evaluated in citrated plasma after addition of 5 pmol/l tissue factor. Fiber thickness within clots was assessed using scanning electron microscopy. Higher G' but not G" was observed for VTE patients taking rivaroxaban (+34%; post hoc, P = 0.029) compared to controls. As reflected by lower G' and G", patients taking rivaroxaban (-19% and -30%; post hoc, P = 0.0013 and P < 0.0001, respectively) formed less stiff and viscous clots compared to VTE patients after OAT withdrawal, also after adjustment for fibrinogen. VTE patients treated with rivaroxaban and VKA had similar clot viscoelastic properties (post hoc, P = 0.85 for G' and P = 0.29 for G"). G' and G" correlated with plasma rivaroxaban concentrations (r = -0.67, P = 0.005 and r = -0.59, P = 0.021, respectively), and the time from the last dose of rivaroxaban intake (r = 0.59, P = 0.02 and r = 0.58, P = 0.022, respectively). G' and G" showed no association with INR in patients on VKAs. G' or G" were not associated with fibrin diameter on scanning electron microscopy images in either group. Our preliminary study shows that both rivaroxaban and VKA improve clot viscoelastic properties in VTE patients, which might contribute to their antithrombotic effects. G' and G" may reflect specific clot physical features, beyond key plasma clot characteristics, which highlights benefits from comprehensive plasma clot analysis in patients with thrombotic diseases.

Influence of Cryopreservation on Structural, Chemical, and Immunoenzymatic Properties of Aortic Valve Allografts.

OBJECTIVES: The problems in preparing (including cryopreservation) and implanting aortic valve allografts (AVAs) is widely elaborated, but some issues need explanation. MATERIAL AND METHODS: Twenty AVAs cryopreserved in dimethylsulphoxide/RPMI solution under -160°C for 1-15 years and 3 controls stored at +4°C up to 2 weeks, from 19 male and 4 female donors, aged 20-51, ±30.8 years, were examined using light (LM), digital (DM), and scanning electron microscopy (SEM), energy dispersion X-ray spectroscopy (EDS), and enzyme-linked immunosorbent assay immunoenzymatic tests (PECAM1, CD34). RESULTS: All AVAs were macroscopically correct. LM revealed normal structure of leaflets but massive endothelial decellularization (±59 cells remained on the surface of 5 mm scraps). DM and SEM demonstrated generally normal collagen structures, but local alterations, probably influenced by freezing-thawing (gaps, separated plates) or being initial phase of native degeneration (grains). EDS detected a little elevated calcium amount in 1 specimen only. The mean PECAM1 and CD34 concentrations were at similar low level in all probes. CONCLUSIONS: Fresh and cryopreservation technologies did not significantly influence the basic properties of AVA leaflets; however, massive endothelial decellularization was present in both groups. Therefore, no endocardial cell activity nor signs of inflammation were observed. These results were independent of donors' age and sex, processing technology, and time of storage of cryopreserved AVAs.

Antiphosphatidylserine/prothrombin (aPS/PT) antibodies are associated with Raynaud phenomenon and migraine in primary thrombotic antiphospholipid syndrome.

Objectives Antibodies to phosphatidylserine/prothrombin complex (aPS/PT) detectable in sera of some patients with antiphospholipid syndrome (APS) have been shown to correlate with thrombosis. However, associations of aPS/PT antibodies with APS related disorders remain unclear. Aim To evaluate whether there are any associations between aPS/PT antibodies and Raynaud phenomenon, migraine and/or valvular lesions in primary thrombotic APS (PAPS). Methods We enrolled 67 consecutive patients (56 women) with thrombotic PAPS (VTE in 80.6%), aged 46.2 ± 13.5 years. The exclusion criteria were: acute coronary syndromes or stroke within preceding 6 months, cancer, severe comorbidities and pregnancy. The IgG and IgM aPS/PT antibodies were determined by ELISA with the cut-off of 30 units. We recorded Raynaud phenomenon, migraine and valvular lesions. Results Positive IgM or/and IgG aPS/PT antibodies were observed in 29 patients (43.3%), with a higher prevalence of IgM antibodies ( n = 27, 40.3%) compared with IgG isotype ( n = 12, 17.9%, p = 0.014). aPS/PT antibodies were observed most commonly in patients with triple aPL ( n = 12, 85.7%) compared with those with double ( n = 5, 35.7%) or single aPL antibodies (n = 12, 30.8%, p = 0.03), with no association with demographics, the ANA titre, the type of thrombotic events or medications. Raynaud phenomenon, migraine and valvular lesions were observed in 15% ( n = 10), 30% ( n = 20) and 18% ( n = 12) of the patients, respectively. Raynaud phenomenon and migraine, but not valvular lesions, were markedly more frequent in PAPS patients presenting with positive aPS/PT antibodies ( n = 10, 34.5% vs. n = 0, 0%; p = 0.0001). Conclusions In PAPS patients aPS/PT antibodies are related to the occurrence of both Raynaud phenomenon and migraine.

[Vascular cerebral malformations in an adult with internal hydrocephalus and great cerebral vein varix undiagnosed in childhood]. / Znieksztalcenia naczyniowe w mózgu osoby doroslej z wodoglowiem wewnetrznym i nierozpoznanym w dziecinstwie zylakiem zyly wielkiej mózgu.

Our material consists of the analysis of the results obtained during the postmortem angiologic research of the brain in a deceased 36-years-old woman treated in Neurosurgical Department of Medical university in Lódz. The patient was diagnosed as follows: Arteriovenous malformation (AVM) in the central region of the brain with giant "aneurysm" of the vein of Gallen. Internal hydrocephalus. The anatomical and angiological investigations were concerned mainly with the vessels of the Willis circle, choroid arteries and their branches both in subarachnoid space and in brain parenchyma--and those regions of the brain where pathological changes were detected angiologically. The reason for the comparative evaluation of the vascular changes was the material prepared earlier in the laboratory and literature data concerning: vascularization od choroid plexus of lateral and III ventricles of the brain and vascular deformities in brains of deceased adult and senile patients. This paper is also an attempt at comparing of the vascular changes in postmortem injection examination to results of radiological studies obtained in living patient (angiography of the internal carotid and vertebral arteries) and CT examination.

[Right eye blindness as the predominating clinical sign in a patient with aortic arch syndrome: a case report]. / Slepota oka prawego jako dominujacy objaw kliniczny u chorego z zespolem luku aorty. Opis przypadku.

A case is described of pulseless disease in 43 years old man with right-sided blindness as the main clinical sign. The brain was supplied with blood via the left vertebral artery. The cerebral circulation was additionally diminished by coexisting subclavian steal-syndrome with reversal of blood flow in the right vertebral artery.

[A case of cerebrospinal rhinorrhea as a postoperative complication of nasal septum surgery]. / Przypadek plynotoku nosowego jako powiklanie po operacji przegrody nosa.

The authors showed the case of nasal liquorrhoea as post operation complication of nasal septum. The patient had plastic operation of perforation in dura mater.

Ultrasound; a method of brain abscess drainage monitoring.

Ultrasound guided percutaneous aspiration was performed in fourteen patients with multiple brain abscesses. A bone defect in the skull served as the site of needle insertion and served to sonographically evaluate the abscesses. Antibiotic therapy was administered in all cases. Repeat drainage was required in 5 cases. There were no complications. In 10 patients complete improvement without CNS lesions was achieved. Three patients suffered from headaches and seizures for a period of 6 weeks following the aspiration. One patient with multiple otogenic abscesses died in spite of multiple efforts to drain the abscesses. Our results demonstrate sonography to be very effective for monitoring brain abscess drainage and follow-up.

[Neurosonography-ultrasonography in diagnosis of the central nervous system]. / Neurosonografia-ultrasonografia w diagnostyce osrodkowego ukøadu nerwowego.

Diagnostic possibilities created by ultrasound in the examination of CNS are discussed. Applications of neurosonography in relation to the diagnosis of brain and spinal cord diseases are listed. Emphasis is on ultrasound monitoring of cerebral biopsy enriching precise diagnosis of CNS.

[Conservative treatment of post-traumatic intracerebellar hematoma]. / Zachowawcze leczenie pourazowych krwiaków sródmózdzkowych.

In previous years many authors stressed the very rare occurrence and difficulties in establishing of early diagnosis in cases of posttraumatic haematomas in the posterior cranial caeity, among them also the intracerebellar ones. The detection rate of this condition has increased greatly after introduction of computed tomography in the diagnosis of complications following craniocerebral trauma, changing also the view on the method of its treatment. Although before the introduction of CT the prevailin view was that all intracerebellar haematomas should be treated sugically the present opinion is that some of them meeting certain criteria (small size, peripheral situation in the cerebellar hemispheres laterally to the midline, absence of symptoms of intracranial hypertension, and the possibility of frequent CT control) may be treated successively without surgical intervention with adwantage to the patient. Two cases are presented in which intracerebellar haematomas were treated conserwatively. The authors review the pertinent literature stressing the criteria which should be considered in the qualification of patients for this management.