4 PHCP311 Hemophilia and other clotting disorders.pptx.pdf

Pharmacotherapy Our Lady of Fatima of Coagulation University College of Pharmacy Disorders Objectives ☐ To explain the pathophysiology of the coagulation disorders ☐ To identify the factors that may induce and potentiate the disease ☐ To discu...

Pharmacotherapy Our Lady of Fatima of Coagulation University College of Pharmacy Disorders Objectives ☐ To explain the pathophysiology of the coagulation disorders ☐ To identify the factors that may induce and potentiate the disease ☐ To discuss the clinical presentation as well the diagnosis and laboratory evaluation. ☐ To create a therapeutic outcome. Coagulation Hemostasis refers to the finely regulated dynamic process of maintaining fluidity of the blood, repairing vascular injury, and limiting blood loss while avoiding vessel occlusion (thrombosis) and inadequate perfusion of vital organs. Thrombus Formation Clotting Factors NOTE: Factor VI has no role in blood coagulation Coagulation Cascade Drugs Involved in Anticoagulation A. Aspirin: Thromboxane A2 inhibitor B. Clopidogrel: ADP inhibitor C. Abciximab: glycoprotein (GP) IIb/IIIa receptor inhibitor D. Warfarin: Vitamin K Epoxide reductase inhibitor ( for CF II, VII, XI, X) E. Heparin, Dalteparin: Antithrombin III activator F. Dabigatran: CF IIa inhibitor G. Rivaroxaban: CF Xa inhibitor H. Alteplase: Tissue Plasminogen Activator Hemophilia Hemophilia Known as Royal disease ▪ A medical condition in which the ability of the blood clot is severely reduced, causing the sufferer to bleed severely from even a slight injury ▪ The condition is typically caused by a hereditary lack of coagulation factor of the FACTOR VIII or FACTOR IX. ☐ Queen Victoria ( Hemophilia B) ☐ Commonly seen in middle aged, elderly and young people who recently gave birth ☐ 1:5000 births (male) ☐ Hemophilia A (CFVIII) 4X> Hemophilia B (CF IX) Hemophilia A Hemophilia A X- linked recessive disorder due to the deficiency of functional clotting factor VIII ☐ Inherited, Spontaneous ☐ S/S: early bruising, inadequate clotting in mild injury; severe cases: spontaneous hemorrhage ☐ S/s of hemorrhage: Anemia, weakness, tachycardia, tachypnea, headache, vomiting, lethargy, hematemesis, melaena, hematuria, epistaxis, mucosal hemorrhages ☐ Dx: CBC, PT, @PTT, factor VIII assay, FVIII inhibitor assay ☐ Management: manage bleeding episodes, use factor replacement products, use of factor inhibitors, plasma- based products, treatment and rehabilitation of joints ( hemophilic synovitis, desmopressin, antifibrinolytics ( tranexamic acid, amino caproic acid)- C/I with px with hematuria ☐ MAB: inhibits factor VIII antibodies: Emicizumab Desmopressin Analog of vasopressin ☐ V1 and V2 receptor: Vasopressin ☐ V2 receptors only: Desmopressin ☐ Induces cAMP activation ☐ cAMP: induces the exocytosis of VWF from storage-> Causes coagulation Acquired Hemophilia Rare but life threatening; bleeding due to autoantibodies against factor VIII ☐ S/S: hemorrhage on skin, muscle, soft tissues and mucous membrane ☐ Dx: ☐ PT, Platelet, Bleeding time-> normal ☐ @PTT: Prolonged ☐ Decreased FVIII, presence of FVIII autoantibodies ☐ Tx: FIIIV infusion, eradication of Autoantibodies by immunosuppression: corticosteroids ☐ MAB: Rituximab ☐ Salvage therapy: Cyclosporin for px with SLE Hemophilia B Christmas disease ☐ Stephen Christmas ☐ Inherited X-linked recessive disorder ☐ FIX deficiency ( 20% of hemophilia ☐ S/S: hemarthrosis ( bleeding of the joints) and hematoma ☐ Dx: CBC: normal to low ☐ Platelet count: normal ☐ FIX assay, fetal screening and HIV, hepatitis screening ☐ VWF and FVIII: differential diagnosis ☐ TX: Factor IX, antifibrinolytics, rituximab and antihemophilic agents Clotting Factor Deficiencies Clotting Factor II deficiency Prothrombin-> thrombin ☐ Deficiency: hypoprothrombinemia/ dysprothrombinemia ☐ Inherited, autoimmune, drug induced, very rare ☐ S/S: hypoprothrombinemia, mucosal bleeding, soft tissue bleeding, hemarthrosis, muscle hematoma, intracranial bleeding, pulmonary hemorrhage, melaena, hematochezia ☐ Autoimmune: Lupus anticoagulant hypoprothrombinemia ☐ Drug: antibiotic induced hypoprothrombinemia ☐ Beta lactam antibiotics due to decreased normal flora-> dec. vitamin K ☐ Cefazolin: thiol content interacts with vitamin K ☐ DX: PT/INR, Assay Factor II, @PTT, factor VII, IX and X ☐ TX: control bleeding, ☐ SLE: give Azathioprine, immunoglobulin, fresh frozen plasma ☐ Warfarin overdose: give Vitamin K, hemostatic agents ( aminocaproic acid: 6- aminohexanoic acid that inhibits fibrinolysis that inhibits TPA substance) Clotting Factor V deficiency ▪ Rare disorder known as Owren’s disease or parahemophilia ▪ - less than 200 cases world wide ▪ Dx: Prolonged: @PTT, PT, thrombin time ▪ Stypven time (Russel viper venom time) ▪ Factor V antigen assay ▪ TX: fresh frozen plasma, blood products Clotting Factor VII deficiency ▪ Rare genetic disorder, due to autosomal recessive manner ▪ Normal @PTT but prolonged PT ▪ Dx: Factor VII deficiency plasma ▪ S/s: bleeding, hemarthrosis, joint swelling, mild fever, joint limitation, bruising with or without trauma, hematoma ▪ Lab test: APTT, PT and platelet ▪ Tx: FVII/ FVIIa replacement, fresh frozen plasma, antifibrinolytics ( Aminocaproic acid) Clotting Factor X deficiency Stuart prower factor, vitamin K dependent serine protease ☐ Aquired: ☐ Congenitally through mutation/ deletion ☐ Liver disease: vit. K reduction ☐ Prophylthiouracil or Vit. K antagonists ☐ Diseases/ drugs that can cause: ☐ Mycoplasma pneumoniae, lupus anticoagulant prothrombinemia, sodium valproate use in epilepsy, leprosy, sever burn in children, topical thrombin administration Patient history: ☐ Severe umbilical cord stump bleeding, Prolonged bleeding upon circumcision, Recurring epistaxis, Hematoma, Hematuria, Post partum bleeding, hemarthrosis Lab test: ☐ Prolonged PT, @PTT and RVVT ☐ Bleeding time is within the reference range Tx: Plasma derivative factor X, vitamin K, Factor X ( coagadex) and factor IX Clotting Factor 12 Deficiency Hageman factor deficiency Begins asymptomatically and usually only discovered during preoperative blood test 1 in 1 million Genetic disorder: gene mutation of F12 gene at the long arm chromosome Common in Asian Complications: increased risk for DVT, increased risk and repeated miscarriage Von Willebrand Disease ▪ Three types ▪ Type 1( mild and common) ▪ 70-80%, dec. VWF and FVII ▪ Type 2( with 4 subtypes) ▪ Type 3 ( rarest and severe, 1: 100,000) ▪ Most common genetic bleeding disorder ▪ Normal range: 5200 IU/dL TYPE 2 VWF disease 20% of cases, normal VWF but does not function normally ▪ 2A: low VWF in blood-> dec. platelet plug ▪ Mucocutaneous bleeding ▪ 2B: increased premature platelet plug in the blood stream instead in the injury ▪ 2M: dec VWF and failure to interact with the platelets ▪ 2D: failure to transport factor VIII to the injury site ▪ Resembles classic hemophilia Type 3 Most severe ( 5% of cases) Complete loss or almost absence of VWF in blood VWF disease Inherited gene mutation: VWF gene in the short arm of chromosome 12 ☐ Autosomal Dominant: ( one gene is mutated, while the other gene is normal) ☐ Type 1 and some type 2 ☐ Autosomal Recessive ( both parents have mutated gene) ☐ Some type 2 and type 3 Pseudo Willebrand disease: gene mutation at the GPIb, autosomal dominant) ☐ S/S: prolonged bleeding, epistaxis, excessive bleeding after surgery, trauma, dental procedures, Lab tests: CBC( for VWF type 2B), coagulation test, VWF antigen test, ristocetin co-factor test, factor VIII clotting test, Molecular gene therapy Treatments: ☐ Desmopressin: for type 1 and 2 ☐ Contraindicated for type 2B: dec. platelet ☐ Replacement therapy for VWF type 2M, 3 and 2B ☐ Aminocaproic acid/ tranexamic acid NOTE: C/I: aspirin, NSAIDs and Blood thinners