Early fibrinogen degradation coagulopathy: a predictive factor of parenchymal hematomas in cerebral rt-PA thrombolysis.

BACKGROUND AND PURPOSE: The purpose of this study was to systematically determine the correlations between the post-thrombolytic changes of hemostasis parameters and the occurrence of early intracerebral hemorrhage (ICH). METHODS: In 72 consecutive patients with cerebral infarcts treated with rt-PA, plasma levels of fibrinogen, plasminogen, alpha2-antiplasmin, factor XIII, fibrin(ogen) degradation products (FDPs) and d-Dimers were measured at baseline, 2 and 24h after thrombolysis. Correlations were studied between the hemostasis events and early (less than 24h) hemorrhagic infarcts (HIs) or parenchymatous hematomas (PH). RESULTS: Of 72 patients, 6 patients (8.3%) had early PHs, 11 (15.3%) had early HIs, and 55 (76.4%) had no bleeding. Early HIs were not linked to any hemostasis parameter at any time. Univariate comparison of patients having early PHs with non-bleeding patients showed hemostasis abnormalities at 2h: high FDP (p=0.01), high Log FDP (p=0.01), low fibrinogen (p=0.01), and low Log fibrinogen (p=0.01). Logistic regression adjusted for age, NIHSS and diabetes confirmed these 2hour predictors: Log FDP (OR: 7.50; CI: 1.26 to 44.61, p=0.03), and Log fibrinogen (OR: 19.32; CI: 1.81 to 205.98, p=0.01). The decrease in fibrinogen less than 2g/L multiplies the odds of early PH by a factor 12.82. CONCLUSION: An early fibrinogen degradation coagulopathy involving an increase of FDP and a massive consumption of circulating fibrinogen is predictive of early parenchymal hematomas, indicating the occurrence of a particularly intense lysis of circulating fibrinogen. These results, if confirmed by future studies, suggest that early assays of fibrinogen and FDP may be useful in predicting the risk of post-thrombolytic intracerebral hematoma.

Post-thrombolysis haemostasis changes after rt-PA treatment in acute cerebral infarct. Correlations with cardioembolic aetiology and outcome.

BACKGROUND: Little is known, in man, in the post-thrombolytic molecular dynamics of haemostasis, particularly the effect of rt-PA on antifibrinolytic components such as alpha2 anti-plasmin and Factor XIII. AIMS AND HYPOTHESIS: The purpose of this study was to systematically determine changes in coagulation and fibrinolytic parameters after thrombolysis with rt-PA during 24h. We also aimed to correlate these parameters with different acute ischemic stroke subtypes and global outcome. METHODS: Eighty consecutive patients with cerebral infarcts treated with rt-PA had their plasma levels of fibrinogen, plasminogen, alpha2-antiplasmin, Factor XIII, fibrin(ogen) degradation products (FDP) and D-Dimers measured at baseline (h0), 2 (h2) and 24h (h24) after initiation of thrombolysis. Correlations between the variations of these components were statistically studied, using the Spearman rank test or the Pearson test. These haemostatic parameters were also compared with cardioembolic and non cardioembolic patients, as well as between poor and favourable outcome patients. RESULTS: Between h0 and h2, a decrease in fibrinogen, plasminogen, alpha2-antiplasmin, and factor XIII was observed, while an increase in FDP and D-Dimers took place. These values returned to the initial levels at h24. At 2h, the decrease in fibrinogen was significantly correlated with that of plasminogen (0.48, p=0.01), alpha2-antiplasmin (0.48, p=0.004), and factor XIII (0.44, p=0.01); the decrease in plasminogen was significantly correlated with those of antifibrinolytic components, factor XIII (0.47, p=0.02) and alpha2-antiplasmin (r=0.77, p<0.001). These variations were independent of NIHSS. Cardioembolic infarcts showed a statistically significant greater h0-h2 decrease in plasminogen (p=0.04) and an h0-h2 increase in FDP (p=0.02). Poor outcome was linked to low plasminogen values at 2 and 24h. CONCLUSIONS: Supposed to be fibrin-specific, rt-PA induces a decrease in circulating fibrinogen, significantly linked to a decrease in plasminogen. A collateral increase in antifibrinolytic agents such as factor XIII and alpha2-antiplasmin is also observed. At 2h, a significant decrease in plasminogen and a significant increase in fibrin(ogen) degradation products (FDP) are observed in cardioembolic infarcts, and appear as early independent predictors of this aetiology. A low plasminogen value at 2h is potentially predictive of poor prognosis at 3months.

Amyloid neuropathy mimicking chronic inflammatory demyelinating polyneuropathy.

INTRODUCTION: Amyloid neuropathy is a rare peripheral neuropathy that classically presents as a progressive sensory neuropathy with prominent autonomic involvement. METHODS: We describe 5 patients with amyloid neuropathy (familial amyloid polyneuropathy or acquired amyloidosis) who were initially mistaken to have chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) based on history, clinical examination, electrodiagnostic studies, and cerebrospinal fluid (CSF) analysis. RESULTS: The diagnosis of CIDP had been retained on clinical and electrophysiological grounds for all patients, but we observed no improvement after immunomodulatory treatment. Nerve biopsy confirmed amyloid deposits in nerves, and molecular genetic analysis showed a mutation of the transthyretin (V30M) gene for 3 patients; the 2 other patients had acquired amyloidosis. CONCLUSIONS: This report emphasizes the need to look for an alternative diagnosis in CIDP patients who do not respond to treatment and to look carefully for symptoms or signs of autonomic involvement in such patients.