fibrin and Intracranial-Aneurysm

This case study provided us with the opportunity to explore the histopathological effects of Guglielmi detachable coil (GDC) therapy on the aneurysm orifice and parent vessel-aneurysm neck interface. This type of study is important to the understanding of the mechanisms of obliteration of aneurysms by GDCs.. The patient presented with a Hunt and Hess Grade III subarachnoid hemorrhage that occurred secondary to the rupture of a small anterior communicating artery aneurysm.. The aneurysm was successfully coiled without complication, but the patient died 36 hours later. We examined the gross and microscopic pathological findings of this GDC-treated anterior communicating artery aneurysm 36 hours after coiling. A discrete membrane composed of fibrin had formed completely across the aneurysm orifice, excluding the aneurysm sac from the circulation. This membrane was contiguous with the parent vessel.. This case represents one of the first examples in humans of the formation of a membrane over the aneurysm orifice after GDC therapy. The formation of this membrane, shown to be composed of fibrin, was found at 36 hours after coiling, which is the earliest time frame at which membrane formation has been noted in either humans or animal models. This fibrin membrane may function both as a scaffold for subsequent endothelialization across the aneurysm neck as well as to isolate the aneurysm from the parent circulation, permitting thrombus within the aneurysm sac to mature to an endovascular scar. The factors contributing to the formation of this membrane and its clinical implications are discussed.

Topics: Aged; Aged, 80 and over; Cerebral Angiography; Embolization, Therapeutic; Endothelium, Vascular; Equipment Design; Fatal Outcome; Female; Fibrin; Humans; Intracranial Aneurysm

Fibrin and fibrinogen degradation products in the cerebrospinal fluid (CSF-FDP) were first studied in a group of 29 patients observed during the first and the second week after subarachnoid hemorrhage (SAH), then in a second group of 26 patients for a total of 55 patients. In the latter group only the first FDP value obtained as soon as possible after SAH was taken in consideration. In the whole series of 55 patients several noteworthy factors were found: 1) FDP determination should be performed as soon as possible after SAH; 2) CSF-FDP at or above 40, 80 micrograms/ml was found both in the patients with severe neurological deficits and in those with cerebral ischemia (statistically significant); 3) the significance of CSF-FDP in patients who rebled was also evaluated. In conclusion CSF-FDP could be considered useful in predicting cerebral ischemia.

Topics: Aneurysm, Ruptured; Biomarkers; Brain Ischemia; Cerebrospinal Fluid Proteins; Consciousness Disorders; Convalescence; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinolysis; Humans; Intracranial Aneurysm; Ischemic Attack, Transient; Recurrence; Rupture, Spontaneous; Severity of Illness Index; Subarachnoid Hemorrhage

Recent studies utilizing shape memory polymer foams to coat embolizing coils have shown potential benefits over current aneurysm treatments. In the current study utilizing a rabbit-elastase aneurysm model, the performance of test article (foam-coated coil [FCC]) and control (bare platinum coils [BPCs]) devices were compared at 30, 90, and 180 days using micro-CT and histological assessments. The host response was measured by identifying the cells regionally present within the aneurysm, and assessing the degree of residual debris and connective tissue. The 3D reconstructions of aneurysms provided context for histologic findings, and aided in the overall aneurysm assessment. At all time points, >75% of the cells categorized in each aneurysm were associated with a bioactive yet biocompatible host response (vs. the remainder of cells that were associated with acute inflammation). The extracellular matrix exhibited a transition from residual fibrin at 30 days to a greater degree of connective tissue at 90 and 180 days. Although the control BPC-treated aneurysms exhibited a greater degree of connective tissue at the earliest time point examined (30 days), by 180 days, the FCC-treated aneurysms had more connective tissue and less debris overall than the control aneurysms. When considering cell types and extracellular matrix composition, the overall host response scores were significantly better in FCC-treated aneurysms at the later time point. Based on the results of these metrics, the FCC device may lead to an advanced tissue remodeling response over BPC occlusion devices.

Topics: Animals; Blood Vessel Prosthesis; Coated Materials, Biocompatible; Fibrin; Foreign-Body Reaction; Humans; Inflammation; Intracranial Aneurysm; Pancreatic Elastase; Platinum; Prosthesis Design; Rabbits; Risk Assessment; Smart Materials; Time Factors; Treatment Outcome; X-Ray Microtomography

Flow diversion aims at treatment of intracranial aneurysms via vessel remodeling mechanisms, avoiding the implantation of foreign materials into the aneurysm sack. However, complex implantation procedure, high metal surface and hemodynamic disturbance still pose a risk for thromboembolic complications in the clinical praxis. A novel fibrin and heparin based nano coating considered as a hemocompatible scaffold for neointimal formation was investigated regarding thrombogenicity and endothelialization. The fibrin-heparin coating was compared to a bare metal as well as fibrin- or heparin-coated flow diverters. The implants were tested separately in regard to inflammation and coagulation markers in two different in vitro hemocompatibility models conducted with human whole blood (n = 5). Endothelialization was investigated through a novel dynamic in vitro cell seeding model containing primary human cells with subsequent viability assay. It was demonstrated that platelet loss and platelet activation triggered by presence of a bare metal stent could be significantly reduced by applying the fibrin-heparin, fibrin and heparin coating. Viability of endothelial cells after proliferation was similar in fibrin-heparin compared to bare metal implants, with a slight, non-significant improvement observed in the fibrin-heparin group. The results suggest that the presented nanocoating has the potential to reduce thromboembolic complications in a clinical setting. Though the new model allowed for endothelial cell proliferation under flow conditions, a higher number of samples is required to assess a possible effect of the coating.

Topics: Cell Adhesion; Cell Proliferation; Cerebrovascular Circulation; Coated Materials, Biocompatible; Drug-Eluting Stents; Fibrin; Hemostasis; Heparin; Heparin Lyase; Human Umbilical Vein Endothelial Cells; Humans; In Vitro Techniques; Intracranial Aneurysm; Materials Testing; Nanostructures; Neointima; Platelet Activation; Tissue Scaffolds; Vascular Remodeling

Aneurysmal subarachnoid hemorrhage (aSAH) has been reported to actuate blood coagulation. Rotational thromboelastometry (ROTEM) is a dynamic hemostatic test that can differentiate various coagulation abnormalities. For example, increased coagulation activity can be detected as a wider amplitude of tracing (maximal clot firmness [MCF]). ROTEM had not been used to evaluate coagulation changes after aSAH. We evaluated the on-going coagulation process in patients with aSAH in a prospective, observational study to compare their ROTEM assay results with the control values obtained from patients undergoing clipping of nonruptured aneurysms.. ROTEM analyses were performed at 12, 24, 48, and 72 hours after the onset of aSAH and compared with the preoperative analyses from the control group. A total of 17 patients with aSAH treated in the intensive care unit and 16 control patients were enrolled.. At 72 hours, EXTEM-MCF was significantly greater in patients with aSAH compared with the baseline values of the control group (68.0 mm [interquartile range (IQR), 66.0-71.0] versus 64.5 mm [IQR, 59.5-66.8]; P = 0.024). This was mainly due to increased fibrin formation and fibrin polymerization. The same comparison in the FIBTEM-MCF analysis yielded similar results (aSAH group, 23.0 mm [IQR, 19.0-25.0] vs. control group, 15.4 mm [IQR, 12.5-17.8], respectively; P = 0.001).. Blood coagulation is activated at 72 hours after aSAH onset, which can be detected by ROTEM EXTEM-MCF analysis. Also, the FIBTEM-MCF was elevated, implying that the relative contribution of fibrin formation and fibrin polymerization is essential.

Topics: Adult; Aged; Blood Coagulation; Female; Fibrin; Humans; Intracranial Aneurysm; Male; Middle Aged; Prospective Studies; Retrospective Studies; Subarachnoid Hemorrhage; Thrombelastography; Time Factors

Treatment of intracranial aneurysms with flow-diverting stents is a safe and minimally invasive technique. The goal is stable embolisation that facilitates stent endothelialisation, and elimination of the aneurysm. However, it is not fully understood why some aneurysms fail to develop a stable clot even with sufficient levels of flow reduction. Computational prediction of thrombus formation dynamics can help predict the post-operative response in such challenging cases. In this work, we propose a new model of thrombus formation and platelet dynamics inside intracranial aneurysms. Our novel contribution combines platelet activation and transport with fibrin generation, which is key to characterising stable and unstable thrombus. The model is based on two types of thrombus inside aneurysms: red thrombus (fibrin- and erythrocyte-rich) can be found in unstable clots, while white thrombus (fibrin- and platelet-rich) can be found in stable clots. The thrombus generation model is coupled to a CFD model and the flow-induced platelet index (FiPi) is defined as a quantitative measure of clot stability. Our model is validated against an in vitro phantom study of two flow-diverting stents with different sizing. We demonstrate that our model accurately predicts the lower thrombus stability in the oversized stent scenario. This opens possibilities for using computational simulations to improve endovascular treatment planning and reduce adverse events, such as delayed haemorrhage of flow-diverted aneurysms.

Topics: Blood Platelets; Embolization, Therapeutic; Fibrin; Humans; Intracranial Aneurysm; Models, Biological; Regional Blood Flow; Stents; Thrombosis

Flow diverters, the specially designed low porosity stents, have been used to redirect blood flow from entering aneurysm, which induces flow stasis in aneurysm and promote thrombosis for repairing aneurysm. However, it is not clear how thrombus develops following flow-diversion treatment. Our objective was to develop a computation model for the prediction of stasis-induced thrombosis following flow-diversion treatment in cerebral aneurysms. We proposed a hypothesis to initiate coagulation following flow-diversion treatment. An experimental model was used by ligating rat's right common carotid artery (RCCA) to create flow-stasis environment. Thrombus formed in RCCA as a result of flow stasis. The fibrin distributions in different sections along the axial length of RCCA were measured. The fibrin distribution predicted by our computational model displayed a trend of increase from the proximal neck to the distal tip, consistent with the experimental results on rats. The model was applied on a saccular aneurysm treated with flow diverter to investigate thrombus development following flow diversion. Thrombus was predicted to form inside the sac, and the aneurysm was occluded with only a small remnant neck remained. Our model can serve as a tool to evaluate flow-diversion treatment outcome and optimize the design of flow diverters.

Topics: Animals; Blood Coagulation; Carotid Artery, Common; Cerebrovascular Circulation; Fibrin; Heart Rate; Image Processing, Computer-Assisted; Intracranial Aneurysm; Kinetics; Male; Models, Biological; Rats, Sprague-Dawley; Stents; Thrombosis

Anosmia is not a rare complication of surgeries that employ the anterior interhemispheric approach. Here, we present a fibrin-gelatin fixation method that provides reinforcement and moisture to help preserve the olfactory nerve when using the anterior interhemispheric approach and describe the results and outcomes of this technique. We analyze the outcomes with this technique in 45 patients who undergo surgery for aneurysms, brain tumors, or other pathologies via the anterior interhemispheric approach. Anosmia occurred in 4 patients (8.8%); it was transient in 2 (4.4%) and permanent in the remaining 2 (4.4%). Brain tumors clearly attached to the olfactory nerve were resected in the patients with permanent anosmia. We found a significant difference in the presence of anosmia between patients with or without lesions that were attaching the olfactory nerve (p = 0.011). Our results suggested that fibrin-gelatin fixation method can reduce the reported risk of anosmia. However, the possibility of olfactory nerve damage is relatively high when operating on brain tumors attaching olfactory nerve.

Topics: Adult; Aged; Craniopharyngioma; Craniotomy; Female; Fibrin; Gelatin; Humans; Intracranial Aneurysm; Male; Meningioma; Middle Aged; Neurosurgical Procedures; Olfaction Disorders; Olfactory Nerve Injuries; Postoperative Complications; Skull Base; Skull Base Neoplasms; Smell; Young Adult

Although coil embolization is known to prevent rebleeding from acutely ruptured cerebral aneurysms, the underlying biological and mechanical mechanisms have not been characterized. We sought to determine if microcoil-dependent interactions with thrombus induce structural and mechanical changes in the adjacent fibrin network. Such changes could play an important role in the prevention of aneurysm rebleeding.. The stiffness of in vitro human blood clots and coil-clot complexes implanted into aneurysm phantoms were measured immediately after formation and after retraction for 3 days using unconfined uniaxial compression assays. Scanning electron microscopy of the coil-clot complexes showed the effect of coiling on clot structure.. The coil packing densities achieved were in the range of clinical practice. Bare platinum coils increased clot stiffness relative to clot alone (Young's modulus 6.9 kPa and 0.83 kPa, respectively) but did not affect fibrin structure. Hydrogel-coated coils prevented formation of a clot and had no significant effect on clot stiffness (Young's modulus 2 kPa) relative to clot alone. Clot age decreased fiber density by 0.2 fibers/µm(2) but not the stiffness of the bare platinum coil-clot complex.. The stiffness of coil-clot complexes is related to the summative stiffness of the fibrin network and associated microcoils. Hydrogel-coated coils exhibit significantly less stiffness due to the mechanical properties of the hydrogel and the inhibition of fibrin network formation by the hydrogel. These findings have important implications for the design and engineering of aneurysm occlusion devices.

Topics: Biomechanical Phenomena; Blood Coagulation; Coated Materials, Biocompatible; Embolization, Therapeutic; Endovascular Procedures; Fibrin; Humans; Intracranial Aneurysm; Models, Cardiovascular

Although several studies have suggested that aneurysmal wall inflammation and laminar thrombus are associated with the rupture of saccular aneurysms, the mechanisms leading to the rupture remain obscure. We performed full exposure of aneurysms before clip application and attempted to keep the fibrin cap on the rupture point. Using these specimens in a nearly original state before surgery, we conducted a pathological analysis and studied the differences between ruptured and unruptured aneurysms to clarify the mechanism of aneurysmal wall degeneration. This study included ruptured (n = 28) and unruptured (n = 12) saccular aneurysms resected after clipping. All of the ruptured aneurysms were obtained within 24 h of onset. Immunostainings for markers of inflammatory cells (CD68) and classical histological staining techniques were performed. Clinical variables and pathological findings from ruptured and unruptured aneurysms were compared. Patients with ruptured or unruptured aneurysms did not differ by age, gender, size, location, and risk factors, such as hypertension, smoking, and hyperlipidemia. The absence or fragmentation of the internal elastica lamina, the myointimal hyperplasia, and the thinning of the aneurysmal wall were generally observed in both aneurysms. The existence of subintimal fibrin deposition, organized laminar thrombus, intramural hemorrhage, neovascularization, and monocyte infiltration are more frequently observed in ruptured aneurysms. Multivariate logistic regression analysis showed that ruptured aneurysm was associated with presence of subintimal fibrin deposition and monocyte infiltration. These findings suggest that subintimal fibrin deposition and chronic inflammation have a strong impact on degeneration of the aneurysmal wall leading to their rupture, and this finding may be caused by endothelial dysfunction.

Topics: Aged; Aged, 80 and over; Aneurysm; Aneurysm, Ruptured; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Female; Fibrin; Humans; Intracranial Aneurysm; Intracranial Hemorrhages; Male; Middle Aged; Muscle Cells; Neovascularization, Pathologic; Neurosurgical Procedures; Risk Factors; Surgical Instruments; Thrombosis

Recurrence after endovascular coiling of intracranial aneurysms is reported in up to 42% of cases and is attributed to the lack of endothelialization across the neck. In this study the authors used a novel tissue engineering approach to promote endothelialization by seeding endothelial progenitor cells (EPCs) within a fibrin polymer injected endovascularly into the aneurysm.. Experimental aneurysms were created in New Zealand White rabbits and were left untreated, surgically clipped, or embolized with platinum coils, fibrin biopolymer alone, or fibrin combined with autologous cultured EPCs.. In aneurysms treated with EPCs, a confluent monolayer of endothelial cells with underlying neointima was demonstrated across the neck at 16 weeks posttreatment, which was not observed with aneurysms treated using the other methods.. This novel technique may address reasons for the limited durability of standard coil embolization and provides further avenues for the development of improved devices for the care of patients with aneurysms.

Topics: Animals; Biopolymers; Cell Movement; Cell Proliferation; Cells, Cultured; Embolization, Therapeutic; Endothelium, Vascular; Endovascular Procedures; Female; Fibrin; Intracranial Aneurysm; Models, Animal; Rabbits; Stem Cell Transplantation; Stem Cells; Tissue Engineering; Treatment Outcome; Vascular Surgical Procedures

Rupture of cerebral aneurysms results in subarachnoid hemorrhage. In many cases, bleeding from aneurysms spontaneously arrests. Although bleeding from cerebral aneurysms has been reported to arrest from outside, bleeding from some aneurysms can arrest in different ways.. Between April 2002 and March 2004, we prospectively investigated mechanisms of spontaneous hemostasis in ruptured aneurysms by macroscopic examination when performing craniotomy and clipping surgeries.. Hemostatic mechanisms were investigated in 247 patients with ruptured aneurysm (77 men, 170 women; age range, 25-95 years). Hemostatic mechanisms were divided into 3 different patterns. In the most common pattern (79.4%), the surface of the aneurysm rupture point was sealed from the outside by a platelet plug or fibrin net (outside-arrest pattern). In some aneurysms (10.1%), a thrombus or platelet plug was attached to the rupture point from inside the aneurysm (inside-arrest pattern). In a very small number of aneurysms (1.6%), a naked thrombus covered the hole made on the arterial wall or small remnant of the aneurysmal dome (bursting pattern) The mechanism remained unclear in the remaining 8.9% of aneurysms. Multivariate analysis revealed that alert consciousness on admission (WFNS grade I) significantly associated with usual hemostasis (outside arrest pattern: OR, 3.8; 95% CI, 1.4-10.0; P = .008). Borderline association with usual hemostasis was found in aneurysms with a size of 5 or smaller than 5 mm (OR, 2.6; 95% CI, 0.99-7.1; P = .052).. The present preliminary study revealed that arrest of bleeding from a ruptured cerebral aneurysm does not always occur from outside the aneurysm. Unusual mechanisms of hemostasis are seen in approximately 12% of ruptured aneurysm. The outside-arrest-pattern aneurysm was more common for smaller aneurysms, and these patients tended to be of better grade. Further studies are necessary to explore the mechanism of hemostasis for ruptured cerebral aneurysms.

Topics: Adult; Aged; Aged, 80 and over; Aneurysm, Ruptured; Blood Coagulation; Blood Platelets; Cerebral Angiography; Cerebral Arteries; Embolization, Therapeutic; Female; Fibrin; Hemostasis; Humans; Intracranial Aneurysm; Male; Middle Aged; Neurosurgical Procedures; Prospective Studies; Subarachnoid Hemorrhage; Subarachnoid Space; Surgical Instruments; Treatment Outcome; Vascular Surgical Procedures

The histopathological characteristics of aneurysms obtained at autopsy or surgery 3 days to 54 months after being treated with Guglielmi detachable coils (GDCs) were assessed.. Seventeen aneurysms were obtained at autopsy and one was removed at surgery. Fourteen were examined histologically with the coils in situ. Naked coils embedded in an unorganized thrombus were found in those aneurysms that had been treated with coils within 1 week earlier. An incomplete replacement of the intraluminal blood clot by fibrous tissue and a partial membranous covering at the aneurysm orifice were observed in those aneurysms that had been treated with coils between 2 and 3 weeks prior to examination. One small aneurysm treated 6 weeks before harvesting showed formation of an endothelium-lined layer of connective tissue at the orifice. Collagen-rich vascularized tissue surrounding the coils was found in an aneurysm removed at surgery 54 months after coil implantation. Interestingly, six (50%) of 12 aneurysms (two small, three large, and one giant) that had been deemed 100% occluded on initial angiography showed tiny open spaces between the coils at the neck on gross examination.. Endothelialization of the aneurysm orifice following placement of GDCs can occur; however, it appears to be the exception rather than the rule. In large aneurysms the process of intraaneurysm clot organization seems to be delayed and incomplete; tiny open spaces between the coils and an incomplete membranous covering in the region of the neck are frequently encountered. Further longitudinal studies are required to establish the spectrum of healing profiles that may direct our efforts in modifying the GDC system to produce a more stable long-term result.

Topics: Adult; Aged; Cerebral Angiography; Collagen; Connective Tissue; Embolization, Therapeutic; Endothelium, Vascular; Female; Fibrin; Fibroblasts; Fibrosis; Follow-Up Studies; Humans; Intracranial Aneurysm; Longitudinal Studies; Macrophages; Male; Middle Aged; Surface Properties; Thrombosis; Wound Healing

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 incidence of chronic hydrocephalus was studied in 39 patients with subarachnoid hemorrhage, who underwent perivascular coating with fibrin glue of cerebral arteries after clipping of aneurysm. A use was made of this procedure in order to prevent vasospasm by keeping the main cerebral arteries away from direct contact with subarachnoid clots. Most cases in this series belonged to group 3 of Fisher's CT grade (33/39, 84.6%). As a result, despite the high CT grade, the incidence of chronic hydrocephalus was as low as 17.9% (7/39), almost in agreement with those of the previous literature. In conclusion, (1) coating with fibrin glue did not increase the incidence of chronic hydrocephalus and (2) intrathecal application of fibrin glue is a promising method in the field of clinical neurosurgery.

Topics: Adhesives; Adult; Aged; Aged, 80 and over; Cerebral Arteries; Chronic Disease; Female; Fibrin; Follow-Up Studies; Humans; Hydrocephalus; Intracranial Aneurysm; Ischemic Attack, Transient; Male; Middle Aged; Subarachnoid Hemorrhage; Time Factors; Tissue Adhesives; Tomography, X-Ray Computed

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

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: Aminocaproates; Blood Coagulation Tests; Fibrin; Fibrinolysin; Fibrinolysis; Humans; Intracranial Aneurysm; Subarachnoid Hemorrhage

Topics: Adult; Aged; Antifibrinolytic Agents; Blood Cell Count; Cerebral Angiography; Cyclohexanecarboxylic Acids; Factor IX; Factor V; Factor VII; Factor X; Female; Fibrin; Fibrinogen; Fibrinolytic Agents; Humans; Hydralazine; Intracranial Aneurysm; Male; Methyldopa; Middle Aged; Phenytoin; Prothrombin; Recurrence; Subarachnoid Hemorrhage

Topics: Blood-Brain Barrier; Chemical Precipitation; Cyclohexanecarboxylic Acids; Depression, Chemical; Electrophoresis, Paper; Fibrin; Fibrinolysis; Humans; Injections, Intravenous; Intracranial Aneurysm; Methods; Rupture; Subarachnoid Hemorrhage; Time Factors