Klinische FragestellungHämostase-Störungen, erblich; Differentialdiagnose

NGS +

Die Blutstillung führt zur Beendigung der Blutung aus einem Blutgefäß und umfasst mehrere miteinander verknüpfte Schritte, die in die Bildung eines Pfropfes münden. Zunächst verengt sich das Blutgefäß und es bildet sich ein vorübergehender Plättchen-Pfropf. Dann wird die Gerinnungskaskade aktiviert (via extrinsischen und intrinsischen Weg), und es bildet sich ein endgültiger Pfropf, der schließlich physiologisch wieder aufgelöst wird (tertiäre Homöostase). Hyper-Koagulation kann zu einer Thrombose führen (wie bei der Faktor-V-Leiden-Mutation, dem Mangel an Protein C und S sowie der Mutationen im Prothrombin-Gen etc.), während Hypo-Koagulation eine wirksame Kontrolle der Blutung verhindert (wie bei der Von-Willebrand-Krankheit, der Hämophilie, der disseminierten intravasalen Gerinnung, dem Mangel an Gerinnungsfaktoren und den Thrombozyten-Störungen etc.). Unter normalen Umständen besteht ein fein reguliertes Gleichgewicht zwischen dem Gerinnungs-fördernden und dem Gerinnungs-hemmenden Signalweg. Am Gerinnungs-Prozess sind verschiedene zelluläre Komponenten beteiligt, die mit dem Endothel, den Blutplättchen und den Hepatozyten in Verbindung stehen. Zu den wichtigsten Ätiologien von Hämostase-Störungen gehören Traumata und Medikamente, aber auch zahlreiche genetische Ursachen, die sehr vielgestaltig sind. Daher ist ein besonders umfassendes Gen-panel für die Abklärung der genetischen Grundlagen erforderlich. Ein negatives DNA-Testergebnis kann die klinische Diagnose vererbte Hämostase-Störung nicht ausschließen, selbst wenn >100 Gene berücksichtigt werden.

Referenzen: https://search.clinicalgenome.org/kb/affiliate/10028?page=1&size=250&search=

• Alias: Inherited bleeding + platelet disorders
• Alias: Monogenic venous thrombosis, included
• Allelic: Albinism, oculocutaneous, type IV (SLC45A2)
• Allelic: Alzheimer disease, late-onset, susceptibility to (PLAU)
• Allelic: Amyloidosis, familial visceral (FGA)
• Allelic: Angioedema, hereditary, type III (F12)
• Allelic: Bone mineral density variation QTL, osteoporosis (COL1A1)
• Allelic: Colon cancer, advanced, somatic (SRC)
• Allelic: Colon cancer, somatic (PTPRJ)
• Allelic: Deafness, AD 17 (MYH9)
• Allelic: Dystonia, juvenile-onset (ACTB)
• Allelic: Gallbladder disease 4 (ABCG8)
• Allelic: LEOPARD syndrome 1 (PTPN11)
• Allelic: Leukemia, acute myeloid (RUNX1)
• Allelic: Leukemia, acute myeloid, somatic (ETV6)
• Allelic: Leukemia, megakaryoblastic, with/-out Down syndrome, somatic (GATA1)
• Allelic: Lewy body dementia, susceptibility to (GBA)
• Allelic: Lowry-Wood syndrome (RNU4ATAC)
• Allelic: Metachondromatosis (PTPN11)
• Allelic: Microcephalic osteodysplastic primordial dwarfism, type I (RNU4ATAC)
• Allelic: Myhre syndrome (SMAD4)
• Allelic: Myocardial infarction, decreased susceptibility to (F7)
• Allelic: Myocardial infarction, protection against (F13A1)
• Allelic: Myocardial infarction, susceptibility to (ITGB3)
• Allelic: Myopathy, tubular aggregate, 1 (STIM1)
• Allelic: Myopathy, tubular aggregate, 2 (ORAI1)
• Allelic: Neurodevelopmental disorder with/-out early-onset generalized epilepsy (NBEA)
• Allelic: Neutropenia, severe congenital, XL (WAS)
• Allelic: Nonaka myopathy (GNE)
• Allelic: Osteogenesis imperfecta, type I-IV
• Allelic: Pancreatic cancer, somatic (SMAD4)
• Allelic: Parkinson disease, late-onset, susceptibility to (GBA)
• Allelic: Polyposis, juvenile intestinal (SMAD4)
• Allelic: Pregnancy loss, recurrent, susceptibility to, 1 (F5)
• Allelic: Pregnancy loss, recurrent, susceptibility to, 2 (F2)
• Allelic: Roifman syndrome (RNU4ATAC)
• Allelic: Seizures, cortical blindness, microcephaly syndrome (DIAPH1)
• Allelic: Skin/hair/eye pigment. 5, black/nonblack hair; dark/fair skin; dark/light eyes (SLC45A2)
• Allelic: Transcription of plasminogen activator inhibitor, modulator of (SERPINE1)
• Afibrinogenemia, congenital (FGA, FGB, FGG)
• Alpha-2-plasmin inhibitor deficiency (SERPINF1)
• Alpha-2-plasmin inhibitor deficiency (SERPINF2)
• Anemia, XL, with/-out neutropenia and/or platelet abnormalities (GATA1)
• Arthrogryposis, renal dysfunction, and cholestasis 1 (VPS33B)
• Arthrogryposis, renal dysfunction, cholestasis 2 (VIPAS39)
• Baraitser-Winter syndrome 1 (ACTB)
• Bernard-Soulier syndrome, type A1 (recessive] (GP1BA)
• Bernard-Soulier syndrome, type A2 [dominant] (GP1BA)
• Bernard-Soulier syndrome, type B (GP1BB)
• Bernard-Soulier syndrome, type C (GP9)
• Bleeding defect due to defective platelet function (RAP1B)
• Bleeding disorder, platelet-type, 11 (GP6)
• Bleeding disorder, platelet-type, 12 (PTGS1)
• Bleeding disorder, platelet-type, 13, susceptibility to (TBXA2R)
• Bleeding disorder, platelet-type, 15 (ACTN1)
• Bleeding disorder, platelet-type, 16, AD (ITGA2B)
• Bleeding disorder, platelet-type, 16, AD (ITGB3)
• Bleeding disorder, platelet-type, 17 (GFI1B)
• Bleeding disorder, platelet-type, 18 (RASGRP2)
• Bleeding disorder, platelet-type, 20 (SLFN14)
• Bleeding disorder, platelet-type, 21 (FLI1)
• Bleeding disorder, platelet-type, 8 (P2RY12)
• Budd-Chiari syndrome (F5)
• Caffey disease (COL1A1)
• Chediak-Higashi syndrome )LYST)
• Combined factor V + VIII deficiency (LMAN1)
• Combined osteogenesis imperfecta + Ehlers-Danlos syndrome 1 (COL1A1)
• Congenital disorder of glycosylation, type IIf (SLC35A1)
• Deafness, AD 1, with/-out thrombocytopenia (DIAPH1)
• Deep venous thrombosis, protection against (F9)
• Dysfibrinogenemia, congenital (FGA, FGB, FGG)
• Dysplasminogenemia (PLG)
• Dysprothrombinemia (F2)
• Ehlers-Danlos syndrome, arthrochalasia type, 1 (COL1A1)
• Ehlers-Danlos syndrome, classic type, 1 (COL5A1)
• Ehlers-Danlos syndrome, classic type, 2 (COL5A2)
• Ehlers-Danlos syndrome, musculocontractural type 1 (CHST14)
• Erythrokeratodermia variabilis et progressiva 4 (KDSR)
• Factor V + factor VIII, combined deficiency of (MCFD2)
• Factor V deficiency (F5)
• Factor VII deficiency (F7)
• Factor X deficiency (F10)
• Factor XI deficiency, AD + AR (F11)
• Factor XII deficiency (F12)
• Factor XIIIA deficiency (F13A1)
• Factor XIIIB deficiency (F13B)
• Fletcher factor (prekallikrein) deficiency (KLKB1)
• Gastrointestinal ulceration, recurrent, with dysfunctional platelets (PLA2G4A)
• Gaucher disease, perinatal lethal (GBA)
• Gaucher disease, type I-III, IIIC (GBA)
• Ghosal hematodiaphyseal syndrome (TBXAS1)
• Giant platelet disorder, isolated (GP1BB)
• Glanzmann thrombasthenia (ITGA2B)
• Glanzmann thrombasthenia (ITGB3)
• Gray platelet syndrome (NBEAL2)
• Hemolytic uremic syndrome, atypical, susceptibility to, 6 (THBD)
• Hemophagocytic lymphohistiocytosis, familial, 5 (STXBP2)
• Hemophilia A (F8)
• Hemophilia B (F9)
• Hermansky-Pudlak syndrome 1 (HPS1)
• Hermansky-Pudlak syndrome 10 (AP3D1)
• Hermansky-Pudlak syndrome 2 (AP3B1)
• Hermansky-Pudlak syndrome 3 (HPS3)
• Hermansky-Pudlak syndrome 6 (HPS6)
• Hermansky-Pudlak syndrome 7 (DTNBP1)
• Hermansky-Pudlak syndrome 8 (BLOC1S3)
• Hermansky-Pudlak syndrome 9 (BLOC1S6)
• High molecular weight kininogen deficiency (KNG1)
• Hyperfibrinolysis, familial, due to increased release of PLAT (PLAT)
• Hypodysfibrinogenemia, congenital (FGA)
• Hypofibrinogenemia, congenital (FGB, FGG)
• Hypoprothrombinemia (F2)
• Immunodeficiency 10 (STIM1)
• Immunodeficiency 71 with inflammatory disease + congenital thrombocytopenia (ARPPC1B)
• Immunodeficiency 9 (ORAI1)
• Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome (SMAD4)
• Kininogen deficiency (KNG1)
• Leukemia, juvenile myelomonocytic, somatic (PTPN11)
• Leukocyte adhesion deficiency, type III (FERMT3)
• Macrothrombocytopenia, AD, TUBB1-related (TUBB1)
• Macrothrombocytopenia, granulocyte inclusions with/-out nephritis/sensorin. hearing loss (MYH9)
• Multidrug resistance-associated protein 4 (ABCC4)
• Myelofibrosis with myeloid metaplasia, somatic (MPL)
• Nonarteritic anterior ischemic optic neuropathy, susceptibility to (GP1BA)
• Noonan syndrome 1 (PTPN11)
• Plasminogen activator inhibitor-1 deficiency (SERPINE1)
• Plasminogen deficiency, type I (PLG)
• Platelet disorder, familial, with associated myeloid malignancy (RUNX1)
• Platelet disorder, macrothrombocytopenia [panelapp] (TPM4)
• Platelet prostaglandin-endoperoxidase synthase-1 deficiency (PTGS1)
• Pseudoxanthoma elasticum-like disorder with multiple coagulation factor deficiency (GGCX)
• Purpura, posttransfusion (ITGB3)
• Quebec platelet disorder (PLAU)
• Radioulnar synostosis with amegakaryocytic thrombocytopenia 1 (HOXA11)
• Radioulnar synostosis with amegakaryocytic thrombocytopenia 2 (MECOM)
• Scott syndrome (ANO6)
• Sialuria (GNE)
• Sitosterolemia 1 (ABCG8)
• Sitosterolemia 2 (ABCG5)
• Stormorken syndrome (STIM1)
• Stroke, ischemic, susceptibility to (F2)
• Stroke, ischemic, susceptibility to (F5)
• Takenouchi-Kosaki syndrome (CDC42)
• Telangiectasia, hereditary hemorrhagic, type 1 (ENG)
• Telangiectasia, hereditary hemorrhagic, type 2 (ACVRL1)
• Thrombocythemia 1 (THPO)
• Thrombocythemia 2 (MPL)
• Thrombocytopenia 2 (ANKRD26)
• Thrombocytopenia 3 (FYB1)
• Thrombocytopenia 4 (CYCS)
• Thrombocytopenia 5 (ETV6)
• Thrombocytopenia 6 (SRC)
• Thrombocytopenia with beta-thalassemia, XL (GATA1)
• Thrombocytopenia, AD, 7 (IKZF5)
• Thrombocytopenia, XL (WAS)
• Thrombocytopenia, XL, intermittent (WAS)
• Thrombocytopenia, XL, with/-out dyserythropoietic anemia (GATA1)
• Thrombocytopenia, anemia + myelofibrosis (MPIG6B)
• Thrombocytopenia, congenital amegakaryocytic (MPL)
• Thrombocytopenia, neonatal alloimmune (ITGB3)
• Thrombocytopenia, neonatal alloimmune, BAK antigen related (ITGA2B)
• Thrombocytopenia-absent radius syndrome (RBM8A)
• Thrombophilia due to HRG deficiency (HRG)
• Thrombophilia due to activated protein C resistance (F5)
• Thrombophilia due to antithrombin III deficiency (SERPINC1)
• Thrombophilia due to heparin cofactor II deficiency (SERPIND1)
• Thrombophilia due to protein C deficiency, AD (PROC)
• Thrombophilia due to protein C deficiency, AR (PROC)
• Thrombophilia due to protein S deficiency, AD (PROS1)
• Thrombophilia due to protein S deficiency, AR (PROS1)
• Thrombophilia due to thrombin defect (F2)
• Thrombophilia due to thrombomodulin defect (THBD)
• Thrombophilia, XL, due to factor IX defect (F9)
• Thrombophilia, familial, due to decreased release of PLAT (PLAT)
• Thrombophilia, susceptibility to, due to factor V Leiden (F5)
• Thrombotic thrombocytopenic purpura, hereditary (ADAMTS13)
• Venous thrombosis, protection against (F13A1)
• Vitamin K-dependent clotting factors, combined deficiency of, 1 (GGCX)
• Vitamin K-dependent clotting factors, combined deficiency of, 2 (VKORC1)
• Warfarin resistance (VKORC1)
• Warfarin sensitivity (F9)
• Wiskott-Aldrich syndrome (WAS)
• von Willebrand disease, platelet-type (GP1BA)
• von Willebrand disease, types 1, 2A, 2B, 2M, 2N, 3 (VWF)