Isolated antiplasmin deficiency presenting as a spontaneous bleeding disorder in a 63-year-old man

Abstract

Spontaneous bleeding in adults is a major problem, and in a significant number of these patients no cause is found. A 63-year-old Caucasian man presented to our hematology clinic with a large hematoma of his left thigh. Initial investigations did not show any conclusive abnormalities of primary or secondary hemostasis. Subsequent tests demonstrated a type 1 deficiency of antiplasmin. Treatment with low doses of epsilon-aminocaproic acid resulted in resolution of the hematoma and control of bleeding. We sought to determine the cause of the patient's isolated antiplasmin deficiency but no explanation was found. Three heterozygous polymorphisms were identified in his antiplasmin gene, ruling out major gene deletions. Each of these three polymorphisms has been previously reported in healthy blood donors. Finally, since response to antifibrinolytics can be dramatic, deficiencies of antiplasmin must be considered in patients presenting at any age with a spontaneous bleeding disorder.

Characterization of a large cohort of patients with unclassified bleeding disorder; clinical features, management of haemostatic challenges and use of global haemostatic assessment with proposed recommendations for diagnosis and treatment

“…Not all laboratory investigations were performed on all patients including ThromboGenomics. Testing for platelet release, electron microscopy, flow cytometry and hyperfibrinolytic disorders (eg alpha‐2 antiplasmin deficiency or plasminogen activator‐1 deficiency), which can cause bleeding disorders, was not performed . In reality, there is a limit to the number of investigations that can be performed and the Vienna Bleeding Biobank have recently described the investigation of bleeding of unknown cause .…”

α2‐Antiplasmin and its deficiency: fibrinolysis out of balance

“…Intramedullary haematomas have not been described. Symptoms may increase with age as a result of falling plasma levels, sometimes erupting a new in elderly patients with heterozygous deficiency [34].…”

“…The real prevalence of the disease is unknown; approximately 40 cases have been reported to date [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33]. In the few patients for whom the molecular defect has been defined, mutations have variously resulted in impaired intracellular transport, decreased activity because of an abnormal protein, and absence of the protein [6,34]. Consanguinity is common in families with homozygous deficiency.…”

Increased plasmin‐α2‐antiplasmin levels indicate activation of the fibrinolytic system in systemic amyloidoses

“…Plasmin is a serine protease that mediates proteolysis of many substrates, including fibrin. Increased plasmin activity has previously been implicated in bleeding [24–30]. Accumulating protein deposits in systemic amyloidosis patients share the structural characteristics that activate plasmin formation and their amyloidogenic progenitors are present in plasma [31,32].…”