Ondřej Zapletal

CHANGES IN HEMOCOAGULATION IN ACUTE STROKE PATIENTS AFTER ONE-HOUR SONO-THROMBOLYSIS USING A DIAGNOSTIC PROBE

The aim was to monitor the changes in hemocoagulation parameters in acute ischemic stroke (AIS) patients after sono-thrombolysis of the occluded middle cerebral artery using a duplex transcranial probe with 2.0-MHz frequency in Doppler mode. Sixteen AIS patients indicated for intravenous thrombolysis (IVT) (8 males; mean age 68.3 +/- 7.1 y) and 16 AIS patients contraindicated for IVT (11 males; mean age 67.9 +/- 7.9 y) were randomized for sono-thrombolysis (8 + 8 patients) or standard treatment (control group) (8 + 8 patients). The significant decrease of plasminogen activator inhibitor-1, plasminogen and alpha-2-antiplasmin activity by a mean of 60, 32 and 24%, respectively, and the increase of tissue plasminogen activator by a mean of 56% was found after sono-thrombolysis when compared with control group (p < 0.0125); these changes were more evident in patients treated with a combination of sono-thrombolysis and IVT (79, 38, 50 and 82%, respectively) than in patients treated by sono-thrombolysis alone (34, 13, 17 and 30%, respectively).

Novel homozygous fibrinogen Aα chain truncation causes severe afibrinogenemia with life threatening complications in a two-year-old boy.

Congenital afibrinogenemia is very rare inherited disease characterized by the absence of plasma fibrinogen [1]. Afibrinogenemia is most frequently caused by mutation in the Aα chain, and less frequently in the Bβ chain. Approximately 102 cases of afibrinogenemia have been described worldwide, of which 78 in the Aα chain, 21 in the Bβ chain, and 11 in the γ chain, respectively [2]. The most commonly described causes of afibrinogenemia have been deletions, insertions, and nonsense mutations causing the insertion of a stop codon. The most common clinical manifestation is serious bleeding. The patient is a twoyear-old boy born in 2011, which since birth has presentedwith serious bleeding. The surgical reconstruction of a cleft lip and palate, completed on the third day of his life, was followed by serious bleeding from his wounds. During the first six months of the boy’s life, hematomas and bleeding occurred around an early erupted, supernumerary tooth. When the boy was 11 months old intracranial bleeding was confirmed by brain CT scan,which showed an old epidural hematoma in the occipital region, with areas of fresh bleeding and signs of intracranial hypertension potentially affecting his occipital cuneus. A successful urgent surgical evacuation of the hematoma saved the boy’s life. The patient’s parents, who are not aware of consanguinity were healthy and without relevant bleeding history; as well other relatives were available for the study. The patient presented with functional and total fibrinogen level below detection limit, and thrombin and reptilase times were over detection limit of the coagulometer (Table 1). The patient’s parents presented with low fibrinogen levels. Functional fibrinogen testing performed as described earlier [3] revealed no polymerization of the patient’s plasma before fibrinogen prophylaxis induced by either thrombin or reptilase. Polymerization of plasma samples from both parents was significantly decreased (data not shown). Fibrinolysis of the patient’s samples was immeasurable due to lack of fibrinogen in the plasma, fibrinolysis of the patient’s father and mother was normal (data not shown). Sanger sequencing revealed a novel homozygous deletion in the patient’s exon 5 of the FGA gene 6477delA. DNA samples of all available relatives were tested for the deletion; and the patient’s mother, father, maternal grandfather, paternal grandfather an maternal aunt were found to be heterozygous carriers of the deletion. A familial relationship between both the maternal and paternal family lines with the deletion is unknown. At the protein level, the deletion causes a change of the primary structure from codon 300 to 339 (ALGLEG LQPGNLGALDLEVLEAGTLGALELEVLETKTLGA) and creates a premature stop codon at 340 (numbering omitting the signal peptide). This novel, previously not described variant was named fibrinogen Poděšín, according to the typical convention of naming fibrinogen variants.