fibrin and Cerebral-Hemorrhage

Although neuronal cells have long been thought to be the prime target of ischaemic insults, events which occur at the blood-vascular-parenchymal interface are necessary for the initiation of ischaemic tissue injury. This cascade of microvascular events includes fibrin accumulation, endothelium expression of leukocyte adhesion receptors, breakdown of the basal laminae with loss of astrocyte and endothelial cell contacts leading to blood-brain barrier disruption and consequently oedema formation and haemorrhagic transformation. Potential stroke treatments have been studied in the clinic and many have not been particularly successful, probably due to the delicate balance between improved outcome and adverse reactions as well as the window of opportunity for drug treatment after symptom onset. The only acute intervention trial demonstrating any benefit in patients was that of intravenous tissue plasminogen activator (tPA), administered within 3 h of the onset of symptoms of ischaemic stroke. Such treatment improved clinical outcome at 3 months, although there was an increased incidence of symptomatic haemorrhage [New Engl. J. Med. 333 (1995) 1581]. The recent progress made in defining the mechanisms involved in the initiation of ischaemic events, as described in this review, may lead to the identification of new strategies for intervention in the ischaemic cascade.

Topics: Animals; Blood-Brain Barrier; Brain Ischemia; Cerebral Hemorrhage; Cerebrovascular Circulation; Edema; Endothelium, Vascular; Fibrin; Humans; Microcirculation; Receptors, Leukocyte-Adhesion

Topics: Abortion, Spontaneous; Blood; Blood Coagulation Tests; Blood Platelets; Cerebral Hemorrhage; Ecchymosis; Factor XIII; Factor XIII Deficiency; Female; Fetal Death; Fibrin; Hematoma; Hemorrhage; Hemorrhagic Disorders; Humans; Infant, Newborn; Placenta; Pregnancy; Pregnancy Complications, Hematologic; Umbilical Cord

Echis carinatus is the most important cause of morbidity and mortality from snake bite in Nigeria and in many other parts of the world. Forty-six patients with systemic poisoning by this snake were given echis antivenom made either by the South African Institute for Medical Research (S.A.I.M.R.) or by Behringwerke (North and West African polyvalent antivenom). A simple test of blood coagulability was used to assess whether an adequate neutralizing dose of antivenom had been given. An average of 15.2 ml S.A.I.M.R. antivenom restored normal coagulability permanently in all 23 patients in one group, but in the other group receiving an average dose of 37.9 ml Behringwerke antivenom normal clotting resulted in only 18 out of 23 patients. Local tissue swelling was similar in both groups, but local necrosis occurred in three patients treated with Behringwerke antivenom and in none given S.A.I.M.R. antivenom.

Topics: Acute Disease; Anemia; Antivenins; Blood Coagulation; Cerebral Hemorrhage; Codeine; Epinephrine; Fibrin; Fibrinogen; Hematocrit; Histamine H1 Antagonists; Humans; Hydrocortisone; Nigeria; Prednisone; Shock; Snake Bites; Snake Venoms

Intracerebral hemorrhage (ICH) is a severe type of stroke without effective treatment. The coagulation cascade is activated after blood flows into the brain parenchyma. The conversion of fibrinogen to fibrin is an essential step of coagulation processes, but its influences on neuroinflammation and long-term outcome after ICH have not been adequately studied. Hirudin binds to thrombin and inhibits the conversion of fibrinogen to fibrin. We therefore investigated the impact of hirudin treatment on brain inflammation and long-term outcome of ICH in mice.. Fibrinogen levels were measured in plasma samples from patients with ICH. In mice subjected to collagenase injection, fibrinogen levels were measured in the plasma and brain. The impact of hirudin on neuroinflammation and long-term neurological outcome was determined in ICH mice.. Circulating fibrinogen level was increased in patients with ICH at day 1 and day 4 after onset. In ICH mice, fibrinogen levels in the blood and brain were increased at day 7. Delayed daily administration of hirudin from day 7 to day 28 significantly improved long-term outcome in ICH mice. Hirudin treatment reduced leukocyte accumulation in the brain and shifted microglia toward an anti-inflammatory phenotype. In addition, depletion of microglia in ICH mice diminished the benefit of hirudin in ICH mice.. These results suggest that inhibition of fibrin formation alleviates brain inflammation and improves long-term outcome after ICH.

Topics: Animals; Brain; Cerebral Hemorrhage; Encephalitis; Female; Fibrin; Fibrinogen; Hirudin Therapy; Hirudins; Humans; Male; Mice, Inbred C57BL

Persistent intracerebral hemorrhage (ICH) is a major cause of death and disability after traumatic brain injury (TBI) for which no medical treatment is available. Delayed bleeding is often ascribed to consumptive coagulopathy initiated by exposed brain tissue factor. We examined an alternative hypothesis, namely, that marked release of tissue-type plasminogen activator (tPA) followed by delayed synthesis and release of urokinase plasminogen activator (uPA) from injured brain leads to posttraumatic bleeding by causing premature clot lysis. Using a murine model of severe TBI, we found that ICH is reduced in tPA(-/-) and uPA(-/-) mice but increased in PAI-1(-/-) mice compared with wild-type (WT) mice. tPA(-/-), but not uPA(-/-), mice developed a systemic coagulopathy post-TBI. Tranexamic acid inhibited ICH expansion in uPA(-/-)mice but not in tPA(-/-) mice. Catalytically inactive tPA-S(481)A inhibited plasminogen activation by tPA and uPA, attenuated ICH, lowered plasma d-dimers, lessened thrombocytopenia, and improved neurologic outcome in WT, tPA(-/-), and uPA(-/-) mice. ICH expansion was also inhibited by tPA-S(481)A in WT mice anticoagulated with warfarin. These data demonstrate that protracted endogenous fibrinolysis induced by TBI is primarily responsible for persistent ICH and post-TBI coagulopathy in this model and offer a novel approach to interrupt bleeding.

Topics: Animals; Antifibrinolytic Agents; Brain; Brain Injuries; Cerebral Hemorrhage; Fibrin; Fibrinolysis; Humans; Male; Mice, Inbred C57BL; Mice, Knockout; Mutation; Plasminogen; Plasminogen Activator Inhibitor 1; Protein Binding; Time Factors; Tissue Plasminogen Activator; Tranexamic Acid; Urokinase-Type Plasminogen Activator

Ischaemic stroke is a serious disease with limited therapy options. Glycoprotein (GP)Ib binding to von Willebrand factor (vWF) exposed at vascular injury initiates platelet adhesion and contributes to platelet aggregation. GPIb has been suggested as an effective target for antithrombotic therapy in stroke. Anfibatide is a GPIb antagonist derived from snake venom and we investigated its protective effect on experimental brain ischaemia in mice.. Focal cerebral ischaemia was induced by 90 min of transient middle cerebral artery occlusion (MCAO). These mice were then treated with anfibatide (4, 2, 1 μg·kg(-1) ), injected i.v., after 90 min of MCAO, followed by 1 h of reperfusion. Tirofiban, a GPIIb/IIIα antagonist, was used as a positive control.. Twenty-four hours after MCAO, anfibatide-treated mice showed significantly improved ischaemic lesions in a dose-dependent manner. The mice had smaller infarct volumes, less severe neurological deficits and histopathology of cerebrum tissues compared with the untreated MCAO mice. Moreover, anfibatide decreased the amount of GPIbα, vWF and accumulation of fibrin(ogen) in the vasculature of the ischaemic hemisphere. Tirofiban had similar effects on infarct size and fibrin(ogen) deposition compared with the MCAO group. Importantly, the anfibatide-treated mice showed a lower incidence of intracerebral haemorrhage and shorter tail bleeding time compared with the tirofiban-treated mice.. Our data indicate anfibatide is a safe GPIb antagonist that exerts a protective effect on cerebral ischaemia and reperfusion injury. Anfibatide is a promising candidate that could be beneficial for the treatment of ischaemic stroke.

Topics: Animals; Bleeding Time; Blood Platelets; Brain Ischemia; Cell Count; Cerebral Hemorrhage; Crotalid Venoms; Dose-Response Relationship, Drug; Fibrin; Infarction, Middle Cerebral Artery; Lectins, C-Type; Male; Mice; Platelet Glycoprotein GPIb-IX Complex; Protective Agents; Reperfusion Injury; Stroke; Tirofiban; Tyrosine; von Willebrand Factor

Fibrin clot formation is important in acute intracerebral hemorrhage (ICH). We investigated plasma fibrin clot characteristics in acute ICH compared with acute ischemic stroke (IS) and nonstroke conditions.. In the 3 studied groups, we analyzed plasma fibrin clot phenotype and its association with clinical stroke presentation.. Compared with controls, in patients with acute strokes, fibrin clots presented with lower clot permeability, longer lysis time, and higher maximum clot absorbance (for all, P<0.001). In ICH patients compared with IS patients, only lysis time was shorter by 13% (P<0.001). In the ICH group, neurological deficit correlated significantly (P<0.05) with clot compaction, and the rate of increase in d-dimers released from clots, whereas initial hematoma volume correlated with lag phase of fibrin formation on turbidimetry and compaction (P<0.05).. In both types of acute strokes, fibrin clot properties are altered: denser fibrin clots are relatively resistant to lysis. In acute ICH, fibrin clots are more susceptible to tissue plasminogen activator-mediated lysis compared with in IS, which might affect ICH pathogenesis.

Topics: Aged; Aged, 80 and over; Cerebral Hemorrhage; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinolytic Agents; Humans; Intracranial Thrombosis; Male; Middle Aged; Phenotype; Stroke; Tissue Plasminogen Activator; Treatment Outcome

We measured the time-dependent change of computed tomography (CT) values for a blood sample in a syringe during 20 days expecting that the (average, maximum) CT values may be used to estimate the elapsed time after hemorrhage. The average CT value (CT(ave)) rapidly increased for the first 50 min. The maximum CT value (CT(max)) increased step by step to take the largest value (82.4 HU) one day later, and subsequently the CT(max) decreased slowly to become 72.0 HU 20 days later. We conclude that the rapid increase of the CT(ave) at the beginning is due to the fibrin generation, the increase of the CT(max) is a result of the formation of the fibrin net, and the subsequent decrease of CT(max) is caused by fibrinolysis. Tentative experimental formula for the time-dependent CT(max) change at each increasing stage and decreasing stage are given to estimate the elapsed time after hemorrhage.

Topics: Biomarkers; Blood Coagulation; Cerebral Hemorrhage; Fibrin; Hemoglobins; Time Factors; Tomography, X-Ray Computed

Brain derived neurotrophic factor (BDNF) has been shown to ameliorate recovery after intracerebral hemorrhage (ICH). The injured brain tissue after ICH is surrounded by hematoma formed from hemorrhage. Fibrin is abundant in hematoma, which could be a binding target for BDNF. In this work, we have fused a fibrin-binding domain (FBD) to BDNF (FBD-BDNF), and results demonstrate that FBD-BDNF has specific binding ability to fibrin and is retained in hematoma. Using the rat ICH model induced by bacterial collagenase, injected FBD-BDNF has been concentrated and retained at the hematoma. FBD has facilitated BDNF to exert targeting neuroprotective effect to the injured brain tissue around the hematoma after ICH. FBD-BDNF has significantly reduced the hemotoma volume, reduced tissue loss, promoted neural regeneration, and improved the rat behavioral performance.

Topics: Animals; Brain-Derived Neurotrophic Factor; Cerebral Hemorrhage; Delayed-Action Preparations; Disease Models, Animal; Fibrin; Hematoma; Humans; Immunohistochemistry; Magnetic Resonance Imaging; Motor Activity; Nerve Regeneration; Protein Binding; Rats; Rats, Sprague-Dawley; Recovery of Function

We evaluated the neuroprotective effect of UK-279,276 (also referred to as recombinant neutrophil inhibitory factor), a selective CD11b/CD18 antagonist, in combination with thrombolytic therapy on focal cerebral ischemia.. Male Wistar rats (n=88) were subjected to embolic middle cerebral artery occlusion. Animals were randomly assigned to the following groups (n=11 in each group): vehicle treatment alone at 2 or 4 hours, UK-279,276 treatment alone at 2 or 4 hours, recombinant human tissue plasminogen activator (rhtPA) treatment alone at 2 or 4 hours, or the combination of UK-279,276 and rhtPA at 2 or 4 hours. Infarct volume, neurological function, hemorrhagic transformation, neutrophil accumulation, and parenchymal fibrin deposition were measured 7 days after middle cerebral artery occlusion.. Treatment with UK-279,276 significantly (P<0.05) improved neurological severity scores, an index of neurological functional deficit, but had no effect on infarct volume compared with vehicle-treated animals. Treatment with rhtPA alone at 2 but not 4 hours significantly (P<0.05) reduced infarct volume and improved neurological function compared with vehicle-treated animals. Combination treatment with UK-279,276 and rhtPA at 2 or 4 hours significantly (P<0.01) reduced infarct volume and enhanced recovery of neurological function compared with control. Neutrophil accumulation and fibrin deposition in the brain parenchyma of combination-treated rats at 2 and 4 hours after stroke were significantly reduced (P<0.05) compared with corresponding vehicle-treated control groups. The neuroprotective effect of the combined treatments was superior to the additive effects from each treatment of rhtPA or UK-279,276 alone.. These data suggest that the combination treatment with UK-279,276 and rhtPA may extend the window of thrombolytic therapy for the acute treatment of stroke.

Topics: Animals; Body Weight; Brain; CD11b Antigen; Cerebral Hemorrhage; Disease Models, Animal; Fibrin; Glycoproteins; Helminth Proteins; Humans; Infarction, Middle Cerebral Artery; Intracranial Embolism; Male; Membrane Proteins; Neurologic Examination; Neuroprotective Agents; Peroxidase; Rats; Rats, Wistar; Recombinant Proteins; Severity of Illness Index; Stroke; Tissue Plasminogen Activator

Thrombin-induced clots used in experimental thromboembolic stroke differ from clots forming spontaneously under clinical conditions. We investigated whether this difference influences the efficacy and outcome of thrombolytic treatment.. In rats, the middle cerebral artery was occluded by intracarotid injection of fibrin-rich clots, prepared either according to established methods by adding thrombin to freshly drawn arterial blood or by spontaneous coagulation. The mechanical properties of clots were determined in vitro by elasticity and plasticity tests. One hour after embolism, thrombolysis was started by intra-arterial application of recombinant tissue plasminogen activator (rtPA) (10 mg/kg). Treatment efficacy was monitored by MR measurements of blood perfusion, apparent diffusion coefficient (ADC), T2 relaxation time and blood-brain barrier permeability, and by pictorial measurements of ATP and pH.. Thrombin-induced clots were classified as elastic, and spontaneously forming clots were classified as plastic. Middle cerebral artery embolism with thrombin-induced or spontaneously forming clots led to similar reduction of perfusion and ADC, but rtPA treatment efficacy differed greatly. In the spontaneously forming clot group, blood perfusion returned to or above control within 2 hours, ADC and ATP normalized, tissue pH exhibited alkalosis, and T2 and blood-brain barrier permeability did not change. In the thrombin-induced clot group, in contrast, blood reperfusion was delayed, ADC and ATP remained reduced, tissue pH was acidic, and edema developed, as reflected by increased T2 and blood-brain barrier permeability.. rtPA-induced thrombolysis promotes rapid reperfusion and tissue recovery in animals embolized with spontaneously forming clots but not in those embolized with thrombin-induced clots. This difference is explained by the different mechanical and possibly molecular consequences of clot preparation and must be considered for the interpretation of thrombolysis experiments.

Topics: Adenosine Triphosphate; Animals; Blood-Brain Barrier; Brain; Cerebral Hemorrhage; Cerebrovascular Circulation; Disease Models, Animal; Disease Progression; Elasticity; Extravasation of Diagnostic and Therapeutic Materials; Fibrin; Gadolinium DTPA; Infarction, Middle Cerebral Artery; Intracranial Thrombosis; Magnetic Resonance Angiography; Male; Rats; Rats, Wistar; Recombinant Proteins; Reperfusion; Stroke; Thrombin; Thrombolytic Therapy; Time Factors; Tissue Plasminogen Activator; Treatment Outcome

Argatroban, a specific thrombin inhibitor, has been shown to reduce ischemic lesion size after focal cerebral ischemia in rats. In addition, recombinant tissue plasminogen activator (rtPA) has been shown to reduce ischemic lesion size in both rats and humans if given within 3 hours of symptom onset. We tested the hypothesis that the administration of argatroban with rtPA could extend the treatment window of stroke to 4 hours without increasing gross cerebral hemorrhage rates or reducing efficacy.. Male Wistar rats were subjected to middle cerebral artery (MCA) occlusion by a single fibrin-rich clot. After embolization, rats were administered argatroban at the following dose levels: 2.08, 6.25, and 18.75 microgram . kg(-1). min(-1). In a second experiment, rats received argatroban (6.25 microgram . kg(-1). min(-1)) or argatroban in combination with rtPA 4 hours after MCA occlusion. Tissue sections were then analyzed for lesion volume, gross hemorrhage and fibrin deposition.. The 6.25 microgram. kg(-1). min(-1) dose demonstrated a significant reduction (P<0.05) in lesion volume after 48 hours (27.2+/-6.3%) compared with controls (35.3+/-3.7%). A significant reduction (P<0.05) in lesion volume was observed in the argatroban-plus-rtPA group (17.1+/-10.4%) compared with controls (35.3+/-3.7%). No increase in hemorrhagic transformation was observed. Fibrin deposition in the ipsilateral cortical microvasculature was significantly decreased in the 4-hour combination argatroban-plus-rtPA group compared with the controls (P<0.05).. This study demonstrates that the combination of argatroban and rtPA extends the window of opportunity for treatment of stroke to 4 hours without increasing hemorrhagic transformation.

Topics: Animals; Antithrombins; Arginine; Brain Ischemia; Cerebral Hemorrhage; Dose-Response Relationship, Drug; Fibrin; Incidence; Infarction, Middle Cerebral Artery; Intracranial Embolism; Male; Pipecolic Acids; Rats; Rats, Wistar; Recombinant Proteins; Stroke; Sulfonamides; Time Factors; Tissue Plasminogen Activator

We report the first case in which a fluid-blood interface was identified at autopsy in a patient with acute intracerebral hematoma on anticoagulant therapy. Anticoagulation may be one of the major factors contributing to the production of an intracerebral blood sedimentation level.

Topics: Aged; Anticoagulants; Blood Sedimentation; Blood-Brain Barrier; Brain; Cerebral Hemorrhage; Fibrin; Heart Valve Prosthesis Implantation; Hematoma; Humans; Male; Mitral Valve Stenosis; Postoperative Complications; Warfarin

Treatment options in acute stroke are limited by a dearth of safe and effective regimens for recanalization of an occluded cerebrovascular tributary, as well as by the fact that patients present only after the occlusive event is established. We hypothesized that even if the site of major arterial occlusion is recanalized after stroke, microvascular thrombosis continues to occur at distal sites, reducing postischemic flow and contributing to ongoing neuronal death. To test this hypothesis, and to show that microvascular thrombosis occurs as an ongoing, dynamic process after the onset of stroke, we tested the effects of a potent antiplatelet agent given both before and after the onset of middle cerebral arterial (MCA) occlusion in a murine model of stroke. After 45 min of MCA occlusion and 23 h of reperfusion, fibrin accumulates in the ipsilateral cerebral hemisphere, based upon immunoblotting, and localizes to microvascular lumena, based upon immunostaining. In concordance with these data, there is a nearly threefold increase in the ipsilateral accumulation of 111In-labeled platelets in mice subjected to stroke compared with mice not subjected to stroke. When a novel inhibitor of the glycoprotein IIb/IIIa receptor (SDZ GPI 562) was administered immediately before MCA occlusion, platelet accumulation was reduced 48%, and fibrin accumulation was reduced by 47% by immunoblot densitometry. GPI 562 exhibited a dose-dependent reduction of cerebral infarct volumes measured by triphenyltetrazolium chloride staining, as well as improvement in postischemic cerebral blood flow, measured by laser doppler. GPI 562 caused a dose-dependent increase in tail vein bleeding time, but intracerebral hemorrhage (ICH) was not significantly increased at therapeutic doses; however, there was an increase in ICH at the highest doses tested. When given immediately after withdrawal of the MCA occluding suture, GPI 562 was shown to reduce cerebral infarct volumes by 70%. These data support the hypothesis that in ischemic regions of brain, microvascular thrombi continue to accumulate even after recanalization of the MCA, contributing to postischemic hypoperfusion and ongoing neuronal damage.

Topics: Animals; Benzylamines; Bleeding Time; Blood Platelets; Cerebral Hemorrhage; Cerebral Infarction; Fibrin; Functional Laterality; Intracranial Embolism and Thrombosis; Male; Mice; Mice, Inbred C57BL; Microcirculation; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Reperfusion

Cerebral amyloid angiopathy (CAA) is known to be associated with intracerebral hemorrhage in the elderly. In this study we demonstrated that, among 101 cases with intracerebral hemorrhages found in 1000 consecutive autopsied cases (average age, 82.9 years) at a geriatric hospital, CAA accounted for 10.9% of them (31.0% of lobar and 14.3% of cerebellar hemorrhages). Immunohistochemically, the cerebrovascular amyloid was positive for beta/A4 peptide, and less intensely for cystatin C. The CAA-related hemorrhages were characteristically located near the cortical surface and ruptured into the subarachnoid space. No mutation of the amyloid precursor protein gene or the cystatin C gene was detected in these cases. From the observation of 500 serial sections containing amyloid-laden vessels of a patient with CAA-related hemorrhage, it was suggested that the hemorrhage occurred at microaneurysms with fibrinoid necrosis, which were found in small arteries in the cerebral cortex. The spatial distribution of CAA was closely associated with that of subpial beta/A4 peptide deposits in the brain, raising the possibility that the cerebrovascular amyloid originates from the brain parenchyma. Finally, the severity of CAA did not seem to be influenced by the inheritance of the epsilon 4 allele of the apolipoprotein E gene, which is known as a risk factor for dementia of the Alzheimer type.

Topics: Aged; Aged, 80 and over; Alleles; Alzheimer Disease; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Aneurysm, Ruptured; Apolipoproteins E; Cerebellar Diseases; Cerebral Amyloid Angiopathy; Cerebral Arteries; Cerebral Cortex; Cerebral Hemorrhage; Cerebrospinal Fluid Proteins; Cystatin C; Cystatins; Cysteine Proteinase Inhibitors; Fibrin; Humans; Immunohistochemistry; Intracranial Aneurysm; Middle Aged; Mutation; Necrosis; Peptide Fragments; Pia Mater; Risk Factors; Subarachnoid Space

The coagulation cascade has a potential role in brain edema formation due to intracerebral hemorrhage. In this study blood and other solutions were injected stereotactically into the right basal ganglia in rats. Twenty-four hours following injection, brain water and ion contents were measured to determine the amount of brain edema. Intracerebral blood resulted in an increase in brain water content. The amount of brain edema surrounding the intracerebral hematoma was reduced by a thrombin inhibitor N alpha-(2-Naphthalenesulfonylglycyl)-4-amidino-DL-phenylalaninep iperidide, (alpha-NAPAP) infused into the hematoma after the clot had been allowed to solidify. The inhibitor did not alter the actual size of the clot mass. An artificial clot composed of fibrinogen, thrombin, and styrene microspheres also produced brain edema. A fibrin clot led to edema formation even in the absence of mass effect provided by the microspheres. The single component responsible for production of brain edema in all these models was thrombin. The edema was formed in response to a fibrinogen-independent pathway. These results indicate that the coagulation cascade is involved in brain edema that develops adjacent to an intracerebral hematoma.

Topics: Animals; Basal Ganglia; Blood Coagulation; Blood-Brain Barrier; Brain Edema; Cerebral Hemorrhage; Fibrin; Male; Rats; Rats, Sprague-Dawley; Thrombin

We investigated the tissue fibrinolytic activity in an experimental model of intracerebral hematoma was developed in the guinea pig. Intracerebral hematoma was created by stereotaxically injecting 0.2 ml autologous blood into the left frontal lobe of a total 63 anesthetized adult male albino guinea pigs (weighing 280-350 gr.). The fibrinolytic activity was studied using conventional histochemical stain techniques. 20 guinea pigs were used for developing the intracerebral hematoma model; in the 43 guinea pigs, the intracerebral hematomas were studied sequentially. Intracerebral hematoma formation failed in 10 of 43 guinea pigs. Three guinea pigs died in the immediate postoperative period. It was diagnosed histopathologically purulent meningitis and ventriculitis in four guinea pigs. Tissue fibrinolytic activity was increased in the meninges and choroid plexus. No fibrinolytic activity was observed a during the first days (1 to 3 days after hematoma production). 3 to 5 days later, fibrinolytic activity was seen in the capillary buds surrounding the hematoma and among the infiltrating mononuclear cells. This activity reached highest levels for 7-14 days following production of the hematoma and decreased after 20 days. In conclusion, tissue fibrinolytic activity associated with neovascularisation and mononuclear cell infiltration appears to be important in lysis of intracerebral hematoma.

Topics: Animals; Cerebral Hemorrhage; Cerebral Ventricles; Erythrocytes; Fibrin; Fibrinolysis; Frontal Lobe; Guinea Pigs; Hemolysis; Male; Neovascularization, Pathologic

The aim of the study was to improve the detection of small hemorrhages with minimal symptoms and of unruptured aneurysms after a subdural and subarachnoid bleeding by the control of the intravascular hemostatic system.. Prospective, open study.. Neurosurgical intensive care unit of a university hospital.. 44 patients undergoing a cranial trepanation. Patients of group 1 (control n = 11) had an intrasellar hypophysoma, patients of group 2 (n = 12) a chronic subdural hematoma without a previous traumatic incident and patients of group 3 (n = 15) a subarachnoid hemorrhage caused by an intracranial aneurysm.. After cranial trepanation changes of plasmatic hemostasis have been assessed by means of immunologically determined parameters of coagulation. The investigation included blood parameters (hemoglobin, hematocrit, thrombocytes), clotting status (prothrombin time, partial thromboplastin time, thrombin time, fibrinogen, plasminogen, antithrombin III [AT III] activity and proteinase inhibitors), as well as immunological methods such as fibrinopeptide A (FPA), thrombin-antithrombin III (TAT), protein C and factor XIII activity (F XIII activity).. In comparison to group 1 (control) a significant difference (p < 0.001) was seen in groups 2 and 3 for thrombin-antithrombin III (TAT), fibrinopeptide A (FPA), protein C, and the antithrombin III activity. Intra- and postoperatively increased TAT levels in groups 2 (16.9 ng/ml) and 3 (21.1 ng/ml) and decreased protein C levels (group 2: 61% and group 3: 58%) demonstrated an intravascular thrombin generation. On account of the elevated FPA levels in groups 2 (6.5 ng/ml) and 3 (5.7 ng/ml) and decreased AT III activity in groups 2 (58%) and 3 (62%), this thrombin generation was only incompletely compensated. Caused by proteolytic thrombin effects, another sign for a thrombin-induced turnover of clotting factors is the significant reduction (p < 0.001) of F XIII activity in groups 2 (40%) and 3 (44%). In comparison to group 1 this significantly reduced F XIII activity in groups 2 and 3 was correlated (r = 0.99) to changes in FPA and TAT plasma levels, an indication of latent chronic clotting activity. No significant difference was found concerning total amount of infusion, intra- and postoperative blood loss and blood parameters. Eight patients (group 2: 5 patients, group 3: 3 patients) showed a rebleeding episode without operative interventions. In these patients increased clotting activity (TAT, FPA, protein C) caused by proteolytic thrombin effects was combined with a factor XIII activity smaller than 40%.. The results of the recent study indicated that immunologically determined TAT, FPA, protein C, factor XIII and AT III activities might serve to improve management in patients with intracranial bleeding events. In view of these parameters the evaluation of risks for a rebleeding is improved. A decrease of the plasma factor XIII activity under 40% associated with a latent clotting activity induced by a thrombin generation caused a higher risk of rebleeding after an initial intracranial bleeding event. The necessity of substituting factor XIII in such cases should be elucidated to minimize risks of rebleeding.

Topics: Aneurysm, Ruptured; Antithrombin III; Blood Coagulation Factors; Blood Coagulation Tests; Cerebral Hemorrhage; Factor XIII; Fibrin; Fibrinogen; Fibrinopeptide A; Hematoma, Subdural; Hemostasis, Surgical; Humans; Intracranial Aneurysm; Peptide Hydrolases; Plasminogen; Postoperative Complications; Protein C; Recurrence; Reference Values; Trephining

We compared the activity of a new long-half-life, fibrin-specific tissue-type plasminogen activator (TPA) variant with that of wild-type TPA in rabbit models of embolic stroke and peripheral bleeding.. In the embolic stroke model. TPA-induced clot lysis is followed by continuous monitoring of a radiolabeled clot lodged in the middle cerebral artery. Twenty-four hours after embolization and treatment with either thrombolytic agent or excipient, the brains are removed, fixed, and evaluated for cerebral hemorrhage. In a parallel template bleeding time experiment, the effects of equipotent doses of the two TPA molecules were measured.. Infusion of wild-type TPA or bolus administration of the TPA variant resulted in dose-dependent clot lysis. The TPA variant was found to be an order of magnitude more potent than wild-type TPA on a milligram-per-kilogram basis. Unlike wild-type TPA, the variant caused less systemic activation of plasminogen (P < .05) and fewer hemorrhagic transformations in this model (P < .05). The TPA variant did not extend template bleeding times.. These findings show that by combining increased fibrin specificity with decreased plasma clearance, it is possible to produce a thrombolytic agent that is more convenient and more potent than wild-tpe TPA. At the same time the significant reduction in hemorrhagic conversions may be attributable to the conservation of systemic plasminogen seen with this molecule.

Topics: alpha-2-Antiplasmin; Animals; Blood Coagulation; Cerebral Hemorrhage; Cerebrovascular Disorders; Dose-Response Relationship, Drug; Fibrin; Fibrinogen; Fibrinolysis; Half-Life; Hemorrhage; Intracranial Embolism and Thrombosis; Male; Plasminogen; Rabbits; Thrombolytic Therapy; Tissue Plasminogen Activator

Thrombocytic, haemostatic and fibrinolytic quantities were investigated in 47 patients with cerebral infarction and 34 patients with cerebral haemorrhage. Sixteen of the infarction patients and ten patients of the haemorrhage group were on acetylsalicylic acid medication. Of the remaining 55 patients without acetylsalicylic medication 21/31 = 67.7% of the patients in the infarction group and 9/24 = 37.5% of the patients in the bleeding group had unphysiologically enhanced ADP-induced platelet aggregation. With regard to the coagulation and fibrinolysis markers no significant differences were found between the two groups. In both groups, coagulation activity markers (fibrin monomer and thrombin-antithrombin III), as well as D-dimers were significantly higher than in controls in a high proportion of cases. In 5/47 of the infarction patients and in 3/34 of the haemorrhage patients the fibrin monomer levels were elevated to such an extent, that it can be considered as low grade disseminated intravascular coagulation. In the cerebral haemorrhage group, 80.3% of the patients who subsequently died showed a significantly enhanced fibrin monomer concentration, compared with 28.6% of those who survived. The corresponding frequencies for D-dimer were 100% compared with 66.7%. In the cerebral infarction group, the only analytical quantity showing a significant difference between patients with a fatal outcome and those with a non-fatal outcome was ADP (2 mumol/l) induced platelet aggregation (83.3% in the fatal group, 40.0% in the non-fatal group).

Topics: Adenosine Diphosphate; Adult; Aged; Aged, 80 and over; Antithrombin III; Blood Coagulation; Cerebral Hemorrhage; Cerebral Infarction; Female; Fibrin; Fibrinolysis; Humans; Male; Middle Aged; Platelet Activation; Platelet Aggregation; Prognosis; Thrombin

A 63-year-old woman presented with extensive bruising. An inhibitor to factor XIII was detected. Subsequent subcutaneous bruising and soft tissue haemorrhage into the left foot were treated with infusions of pasteurized factor XIII concentrate with good effect. Immunosuppression with cyclophosphamide was attempted but in spite of this she suffered a right cerebral haemorrhage necessitating further intensive therapy with factor XIII concentrate. This overcame the inhibitor, adequate post-infusion factor XIII levels were achieved and she made an excellent recovery. Factor XIII concentrate was well tolerated with no evidence of transmission of hepatitis or HIV infection. The inhibitor appeared to interfere with haemostasis by hindering the fibrin binding site of factor XIII, resulting in interference in clot-solubility tests. Subsequently the inhibitor resolved.

Topics: Blood Coagulation Tests; Cerebral Hemorrhage; Factor XIII; Female; Fibrin; Humans; Immunoglobulin G; Middle Aged

Evidence of damage to cerebral vein walls was sought in 70 cases of multiple sclerosis. Seventy control cases were also examined. The multiple sclerosis cases showed venous intramural fibrinoid deposition (7%), recent haemorrhages (17%), old haemorrhages revealed by haemosiderin deposition (30%), thrombosis (6%) and thickened veins (19%). In all, 41% of all multiple sclerosis cases showed some evidence of vein damage. Occasional control cases showed haemosiderin deposition in the brain but, unlike the multiple sclerosis cases, these were diffuse and almost entirely related to coexistent cardiovascular or cerebrovascular disease. Haemosiderin deposition was common in the substantia nigra and other pigmented nuclei in all cases. It is concluded that the cerebral vein wall in multiple sclerosis is subject to chronic inflammatory damage, which promotes haemorrhage and increased permeability, and constitutes a form of vasculitis.

Topics: Cerebral Hemorrhage; Cerebral Infarction; Cerebral Veins; Cerebrovascular Disorders; Fibrin; Hemosiderin; Humans; Intracranial Embolism and Thrombosis; Iron; Multiple Sclerosis; Vasculitis

The brain stems from 52 corpses were microscopically examined. These cases died as a result of closed head injuries, which were clinically diagnosed and/or diagnosed postmortem as primary brain stem lesions. The morphological changes in these cases were compared with morphological changes in the brain stems of corpses who died from cerebral hemorrhage with additional secondary brain stem lesions. The examinations revealed acidophilic necrosis of the vessel walls in brain stem hemorrhages with fibrin impregnation of the vessel walls. Fibrin penetration to the perivascular space was the basic morphological marker that helped to differentiate between these two groups of cases.

Topics: Adolescent; Adult; Aged; Arteries; Brain Stem; Cerebral Hemorrhage; Child; Fibrin; Humans; Intracranial Pressure; Middle Aged; Muscle, Smooth, Vascular; Necrosis

A combined dynamic examination of 114 patients with strokes of different nature localized in the cerebral hemispheres has shown that the degree of the hemostatic changes depends on the severity of the disease and the stage of the DIC syndrome at the time of examination. Three stages of DIC have been identified: hypercoagulation, incomplete consumption coagulopathy, and marked consumption coagulopathy. Drug correction of hemostatic alterations is possible only at stages I and II. The guidelines of the drug therapy of the DIC syndrome associated with cerebral strokes are presented.

Topics: Adult; Aged; Antifibrinolytic Agents; Brain Ischemia; Cerebral Hemorrhage; Cerebral Infarction; Cerebrovascular Disorders; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinolysis; Humans; Male; Middle Aged; Protease Inhibitors

We report experimental studies showing the relationship of the reflectivity of blood clot to both the red cell mass and the fibrin mesh. The highest amplitude echoes are returned by the fibrin mesh. These studies are compared with clinical examples of the different types of neonatal intracranial haemorrhage, as demonstrated by ultrasound. We conclude that the typical high-amplitude echoes characteristic of intracerebral haemorrhage are primarily due to the amount of fibrin mesh present, and not to the intact red cell mass, as has been previously suggested.

Topics: Blood Coagulation; Cerebral Hemorrhage; Cerebral Ventricles; Chronic Disease; Erythrocyte Volume; Fibrin; Hematoma, Subdural; Humans; Infant, Newborn; Subarachnoid Hemorrhage; Ultrasonography

Cerebral vascular lesions of 26 cases in systemic lupus erythematosus during a period from 1963 to 1978 were examined histologically and the following conclusions were made: 1. The prominent vascular changes of the brain were thrombosis, fibrinoid degeneration, endothelial swelling and proliferation, arteriolosclerosis, and perivascular infiltration of inflammatory cells. 2. From clinico-pathological viewpoints, thrombosis seemed to play an important role in the development of neurological signs. In five cases, characteristic granular or homogeneous thrombi were observed in the small blood vessels including venule. Infarct without proved vascular obstruction but probably due to thrombosis was seen in four cases. The true character of the granular thrombi was not determined, either electronmicroscopically or immunohistochemically. These suggested the presence of a tendency for in situ formation of thrombus. 3. Fibrinoid degeneration seen in four cases mainly affected arterile of less than 50 micrometer in diameter in the cerebral cortex, basal ganglia, and brain stem. This change of arteriole did not play a significant role in neurological signs. 4. Endothelial swelling and proliferation of the small blood vessels were prominent in the cases with thrombosis and fibrinoid degeneration. 5. Perivascular infiltration of the inflammatory cells was observed in about one-half of the cases but its significance was not clear.

Topics: Adolescent; Adult; Blood Vessels; Brain; Brain Diseases; Cerebral Hemorrhage; Cerebral Infarction; Cerebrovascular Disorders; Child; Encephalitis; Endothelium; Female; Fibrin; Humans; Intracranial Arteriosclerosis; Intracranial Embolism and Thrombosis; Lupus Erythematosus, Systemic; Male; Middle Aged

Plasmatic arterionecrosis, the causative lesion of hypertensive cerebral hemorrhage, follows upon medial muscle cell necrosis. The development of medial muscle cell necrosis, the earliest cerebral arterial change seen in hypertensive rats, was inhibited when these animals were fed a cholesterol and lard-supplemented diet. Insudation of fibrin was noted in the arterial intima of hypertensive rats with bilaterally constricted renal arteries. Removal of the constriction induced a fall in the elevated blood pressure and an increase of intimal muscle cells. These were responsible for the dissolution of the deposited fibrin, leading to arteriosclerosis. These myointimal cells may originate from the endothelium. Arterial contraction caused by methoxamine hydrochloride often induced the intrusion of one medial muscle cell into another and increased endothelial permeability. 12-24 h after contraction, the arterial segments showed medial muscle cell necrosis, endothelial desquamation with platelet adhesion, and blood plasma infiltration.

Topics: Animals; Arteriosclerosis; Cerebral Arteries; Cerebral Hemorrhage; Fibrin; Humans; Hypertension; Male; Mesenteric Arteries; Methoxamine; Muscle Contraction; Muscle, Smooth; Necrosis; Rats; Renal Artery

Three cases of intracerebral hemorrhage are described in which there was fibrinoid degeneration of cerebral arteries and arterioles or miliary aneurysms or both. Fibrous balls are shown to be sclerosed true aneurysms. These changes occurred in the absence of malignant hypertension and perhaps in the absence of any hypertension. A further point of interest was the finding of fibrinoid at the site of apparent aneurysm formation in a small artery on the cerebral surface, a location at which miliary aneurysms are not generally thought to form. The presence of intracerebral hemorrhage in all three cases, and the ready demonstration of similar changes in other cases of intracerebral hemorrhage, suggest but do not prove that the fibrinoid degeneration or aneurysm leads to vessel rupture and to hemorrhage itself. Also unsettled is the question of whether miliary aneurysms form only at sites already displaying fibrinoid change. Our data suggest that pre-existing fibrinoid may not be a prerequisite for miliary aneurysm formation.

Topics: Aged; Cerebral Arteries; Cerebral Hemorrhage; Female; Fibrin; Humans; Intracranial Aneurysm; Male; Middle Aged

Topics: Afibrinogenemia; Blood Coagulation Disorders; Blood Coagulation Tests; Brain Injuries; Cerebral Hemorrhage; Disseminated Intravascular Coagulation; Factor V; Factor VIII; Fibrin; Fibrinogen; Humans; Plasma Substitutes

Topics: Adolescent; Adult; Age Factors; Aged; Animals; Blood Coagulation; Body Temperature; Cerebral Hemorrhage; Cerebrospinal Fluid; Child; Child, Preschool; Dogs; Female; Fibrin; Fibroblasts; Haplorhini; Hematoma, Subdural; Humans; Infant; Intracranial Pressure; Male; Middle Aged; Osmotic Pressure; Sex Factors; Subarachnoid Hemorrhage; Subdural Space

Three cases with intracranial lesions developed evidence of disseminated intravascular coagulation which was confirmed at necropsy. The factors engendering this state, including release of potent thromboplastin from neural tissue are discussed and the danger of this intermediary mechanism of disease increasing the mortality of intracranial disease is demonstrated. Careful haematological investigation of all patients with intracranial disease is therefore advised, especially if they manifest evidence of a bleeding tendency.

Topics: Adult; Blood Cell Count; Blood Platelets; Brain Abscess; Brain Injuries; Cerebral Cortex; Cerebral Hemorrhage; Child; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrinogen; Hemoglobinometry; Humans; Kidney; Male; Necrosis; Prothrombin Time; Thrombin

Topics: Adult; Cerebral Hemorrhage; Contraceptives, Oral; Dura Mater; Ethinyl Estradiol; Female; Fibrin; Hematoma; Humans; Intracranial Embolism and Thrombosis; Lynestrenol; Mestranol; Middle Aged; Pia Mater; Sinus Thrombosis, Intracranial; Testosterone; Thrombophlebitis

Topics: Animals; Brain; Cerebral Hemorrhage; Craniotomy; Dogs; Fibrin; Fibrinolysis; Hematoma; Injections; Methods; Punctures; Time Factors

Topics: Apgar Score; Asphyxia Neonatorum; Blood; Cerebral Hemorrhage; Female; Fibrin; Fibrinogen; Fibrinolysis; Gestational Age; Humans; Hyaline Membrane Disease; Hydrogen-Ion Concentration; Infant, Newborn; Obstetric Labor Complications; Oxygen; Partial Pressure; Pregnancy; Pregnancy Complications; Prognosis; Respiratory Distress Syndrome, Newborn; Time Factors

Topics: Adolescent; Adult; Anemia, Hemolytic; Autoantibodies; Autopsy; Brain; Cerebral Hemorrhage; Child; Child, Preschool; Diagnosis, Differential; Female; Fibrin; Humans; Infant; Malaria; Male; Nervous System Diseases; Pigmentation; Seizures

Topics: Autopsy; Blood Cell Count; Blood Coagulation Factors; Blood Coagulation Tests; Blood Platelets; Blood Vessels; Cerebral Hemorrhage; Disseminated Intravascular Coagulation; Erythroblastosis, Fetal; Female; Fibrin; Fibrinogen; Hemoglobins; Hemorrhage; Humans; Infant, Newborn; Liver; Lung; Pregnancy; Retrospective Studies; Subarachnoid Hemorrhage; Thrombin; Thromboplastin

Fifty-two surviving low-birth-weight infants who had low Thrombotest (Owren) results on the first day, together with the same number of matched controls with higher Thrombotest results, were examined for the integrity of their central nervous system. Gross abnormalities were found in 13.5% of the low Thrombotest group compared with 1.9% in the higher group. Minor brain damage syndromes were more common in the low Thrombotest group. The combined brain damage syndromes were 23.1% in the low Thrombotest group compared with 3.8% in the higher group.It is suggested that the causes of the brain damage in the low Thrombotest group are either non-fatal cerebral haemorrhage or intravascular fibrin deposition associated with disseminated intravascular coagulation.

Topics: Birth Weight; Brain Diseases; Cerebral Hemorrhage; Child Development; Child, Preschool; Fibrin; Humans; Hypoprothrombinemias; Infant; Infant, Newborn; Infant, Newborn, Diseases; Intelligence Tests; Intracranial Embolism and Thrombosis; Neurologic Examination; Prognosis

Topics: Abortion, Criminal; Accidents, Traffic; Adult; Animals; Brain; Brain Injuries; Cerebral Hemorrhage; Embolism, Air; Female; Fibrin; Forensic Medicine; Heart Ventricles; Humans; Injections; Intracranial Embolism and Thrombosis; Male; Middle Aged; Pregnancy; Rabbits

Topics: Adrenal Gland Diseases; Adult; Afibrinogenemia; Arteries; Cerebral Hemorrhage; Female; Fetal Death; Fetal Diseases; Fibrin; Humans; Infant, Newborn; Liver Diseases; Portal Vein; Pregnancy; Splenic Diseases; Thromboembolism; Umbilical Arteries; Umbilical Cord

Topics: Blood Coagulation Disorders; Blood Coagulation Tests; Cerebral Hemorrhage; Child; Diagnosis; Enzymes; Factor XIII; Fibrin; Genetics, Medical; Hemarthrosis; Hematoma; Hematoma, Subdural; Hemorrhagic Disorders; Humans; Knee Joint

Topics: Central Nervous System Diseases; Cerebral Hemorrhage; Child; Encephalitis; Fibrin; Hematoma; Hematoma, Subdural; Humans; Hydrocephalus; Intracranial Embolism; Intracranial Embolism and Thrombosis; Meningitis; Pathology

Three ;normal' groups of people-young, middle-aged, and old-have been investigated with regard to the fibrin content and fibrinolytic activity of the blood. The fourth group consisted of middle-aged people who had previously sustained a cerebral vascular accident matched statistically for age with the middle-aged normals. It was concluded that fibrin increases with age but there is an interaction between age and sex, the female having a higher level in the young group and the male a higher level in the middle-aged group. There was no sex difference in the levels of fibrin in the old age group. Fibrinolytic activity increases with age and there is a positive correlation between fibrin and fibrinolytic activity but no age-sex interaction. Those with cerebral vascular accidents tended to have higher fibrin levels and lower fibrinolytic activity but the differences were not statistically significant. There did, however, appear to be an increase in antifibrinolytic activity in the cerebral vascular group.

Topics: Accidents; Aging; Antifibrinolytic Agents; Cerebral Hemorrhage; Female; Fibrin; Fibrinolysis; Humans; Male; Middle Aged; Stroke