Your SlideShare is downloading. ×
Congenital bleeding disorders
Upcoming SlideShare
Loading in...5
×

Thanks for flagging this SlideShare!

Oops! An error has occurred.

×
Saving this for later? Get the SlideShare app to save on your phone or tablet. Read anywhere, anytime – even offline.
Text the download link to your phone
Standard text messaging rates apply

Congenital bleeding disorders

439

Published on

gives an overview of congenital bleeding disorders especially the more common ones - hemophilia and von willebrand disease

gives an overview of congenital bleeding disorders especially the more common ones - hemophilia and von willebrand disease

Published in: Health & Medicine, Technology
0 Comments
0 Likes
Statistics
Notes
  • Be the first to comment

  • Be the first to like this

No Downloads
Views
Total Views
439
On Slideshare
0
From Embeds
0
Number of Embeds
0
Actions
Shares
0
Downloads
43
Comments
0
Likes
0
Embeds 0
No embeds

Report content
Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
No notes for slide
  • Good Morning. I am Dr. Lesaca- Medina.
  • Who knows who this is?
    Who knows who this is? She is responsible for the most common severe congenital bleeding disorder. Queen of England in the … Queen Victoria
  • And these are her descendants who married into every royal family in Europe and spread the disease now known as Hemophilia. The Royal disease.
  • Transcript

    • 1. Congenital Bleeding Disorders Ma. Ysabel Lesaca-Medina, MD Pediatric Hematology-Oncology
    • 2. Prince Leopold Born 1853
    • 3. Princess beatrice, 9th child Princess louise Prince leopold, 8th child
    • 4. Married to Princess Helene: 1882
    • 5. Princess Alice Hemophilia carrier
    • 6. London news: Death of the duke of albany March 27, 1884 Villa Nevada Morphine side effects
    • 7. Prince charles Princess alice
    • 8. Outline  What is and how does hemostasis occur?  How does one evaluate a patient presenting with bleeding?  What are the features of the Congenital Bleeding Disorders?  Hemophilia A, Hemophilia B  Von Willebrand Disease  Platelet function disorders  Rare Coagulation Factor Deficiencies
    • 9. What is Hemostasis ?  Maintenance of fluid blood flow  Prevention of bleeding
    • 10. Hemostasis – 3 stages 1. Vascular – vasoconstriction 1. Platelet (PRIMARY HEMOSTASIS) – Platelet plug formation 1. Coagulation (SECONDARYHEMOSTASIS) – Fibrin thrombus formation – Clotting factors
    • 11. Intact vessel
    • 12. Platelet Phase
    • 13. platelet phase
    • 14. Resting  activated platelets
    • 15. Coagulation phase
    • 16. Fibrin Clot
    • 17. PTT
    • 18. APTT
    • 19. PT
    • 20. TT
    • 21. Factor XIII cross links fibrin
    • 22. Clinical Evaluation of Bleeding patient
    • 23. Clinical History
    • 24. Detailed History  Symptoms:  Epistaxis gum bleeding, easy bruising, menorrhagia, hematuria, GI bleeding (platelet problem)  hemarthrosis, intramuscular bleed (coagulation problem)  Delayed onset bleeding (factor XIII problem)
    • 25. Detailed History Response to hemostatic challenge: circumcision, surgery, phlebotomy, immunization, suture placement/removal Underlying medical conditions :  liver disease, renal failure, vitamin K deficiency Medications:  antiplatelet drugs, anticoagulants, antimetabolites, antibiotics
    • 26. Detailed History  Family history:  similar symptoms  response to hemostatic challenge,  consanguinity  Menorrhagia  > 3 soaked pads /day  Flooding  Hb < 10g/L
    • 27. Physical Examination
    • 28. Physical Examination Petechiae < 2mm Purpura 2mm – 1 cm Hematoma Ecchymoses > 1 cm
    • 29. Physical Examination HEMARTHROSIS
    • 30. Physical Examination INTRAMUSCULAR BLEED, PSOAS
    • 31. Laboratory evaluation
    • 32. Laboratory Evaluation  Initial lab tests  CBC with platelet  PT (extrinsic)- VII, X, V, II, I  PTT (intrinsic)- XII, XI, IX, VIII, X, V,II, I  Further work up:  Thrombin time  PFA, platelet aggregation  Mixing Studies, clotting factor assays, VW antigen tests, urea clot lysis assay
    • 33. DDX, based on initial screen ↑ PT Normal plt, Normal PTT ↑ PTT Normal plt, Normal PT ↑ PT,PTT Normal plt •Early Liver Disease •Early Vit K Def •F VII Def •F VIII def (hemophilia or VWD) •F IX, XI, XII def •Inhibitors •Late Liver Disease •Late Vit K deficiency •Massive Transfusion
    • 34. ↑ PTT, TT Normal PT, Normal plt All normal Platelet dec Heparin - activates AT III  AT III inactivates thrombin - PTT more sensitive to heparin VWD Platelet fxn d/o Mild factor def (VIII, IX, XI, XIII ) Collagen Disorder Vitamin C def CAMT, TAR,BSS WAS, GPS ITP Infection CAMT = Congenital Amegakaryocytic Thrombocytopenia BSS = Bernard Soulier Syndrome TAR = Thrombocytopenia with Absent Radius GPS = Gray Platelet Syndrome WAS = Wiskott Aldrich Syndrome
    • 35. Out Patient Clinic Time
    • 36. 6 year/ M  Needs dental extraction; sent for hematologic clearance  History of easy bruisability  Mother and aunts report easy bruisability and strong menses  2 cousins died during delivery of unknown cause
    • 37.  Labs  CBC Normal  PT Normal  PTT 39.3 (23 – 33 secs)
    • 38. DDX, Normal plt, Normal PT prolonged PTT,  Dec Factor VIII due to  Hemophilia A  VWD  Dec Factor IX, XI, XII  Lupus anticoagulant or other coagulation factor inhibitors
    • 39.  Factor VIII : 0.29 u/ml (0.5 – 1.5 u/ml)  VWF : 1.2 u/ml (0.5 – 1.5 u/ml)
    • 40. Hemophilia A, mild Diagnosis
    • 41. HEMOPHILIA  Essentials  Factor VIII (or IX ) deficiency  X-linked (2/3) or spontaneous mutation (1/3)  Sxs: Bruising, soft tissue bleeding, hemarthrosis  Labs: Prolonged PTT + dec factor VIII (or IX) levels
    • 42. HEMOPHILIA  Most common severe congenital bleeding disorder  Prevalence  Hemophilia A (Factor VIII)  1 / 10,000 males  Hemophilia B (Factor IX)  1 / 50,000 males
    • 43. HEMOPHILIA – severity classification  Factor VIII – reported in units / ml ( 1 unit/ml = 100% factor activity) - Normal range: 0.5 – 1.5 IU/ml (50 – 150%) Classification - Severe (60% of cases) : < 1% factor VIII (spontaneous bleeding) - Moderate : 1 to < 5% - Mild : 5 – 50 % ( only with trauma and surgery)
    • 44. HEMOPHILIA- Lab findings  PTT (normal plt; normal PT)  Dx is confirmed by Factor Assay  F VIII ( with normal VWF ) = Hemophilia A  Dec F IX = Hemophilia B
    • 45. HEMOPHILIA- S/Sx  Severe Hemophiliacs  Usually initial presentation in 1st 2 years of life ( severe bruising and joint bleeds)  40 – 50% present in the 1st month of life  1- 4% present in the neonatal period (birth trauma)
    • 46. HEMOPHILIA  Mild or Moderate  Boys  Trauma related bruising or bleeding  Excessive bleeding following surgery or dental extraction  Girls ( carriers ) ~ Often with Factor VIII < normal  Mild bruising or bleeding  Heavy menstrual periods
    • 47. HEMOPHILIA-Cxs  Hemarthroses  If recurrent  joint destruction  Intracranial hemorrhage  Leading cause of death among hemophilliacs  Intramuscular hematomas  Compartment syndrome  muscle and nerve death ( anterior forearm, anterior tibial compartment)
    • 48. HEMOPHILIA-Cxs • Infection • HIV, Hep B, Hep C • Not at risk, With current donor screening and viral inactivation of factor concentrates, • But still at risk for: • Hepatitis A • Creutzfeld-Jakob Disease • Parvovirus B-19 • Recommend Hep A and Hep B vaccines for all pxs
    • 49. HEMOPHILIA-Cxs • Acquired antibody to Factor VIII • Antibody that inactivates F VIII function • Develops in • 30% of pxs with severe hemophilia • < 5% of Hemophilia B
    • 50. Antibody to factor VIII • Quantified by Bethesda units • 1 Bethesda unit – inactivates 50% of F VIII function • TREATMENT: • < 5 B.U. • Increase dose of F VIII • > 5 BU • Bypass agents: prothrombin complex conc ; FVII • ITI (immune tolerance induction)
    • 51. HEMOPHILIA- Tx General aim of Mx: correct factor VIII to w/in normal limits  prevent or stop bleeding Mild May respond to desmopressin (ADH) - Releases endothelial stores of VWF Most still need exogenous F VIII after
    • 52. HEMOPHILIA-Tx • Factor VIII dose • Non-life/limb threatening bleed • 20 to 30 u/kg  40 – 60% F VIII activity • Large hemarthrosis and life/limb threatening bleed • 50 u/KG  100% F VIII activity • Cryoprecipitate • 100 u F VIII / unit • e.g. 10 kg child –> 20 u/kg = • 200 u F VIII -> 2 u cryoppt) • (FFP (contains factor IX) – used for Hemophilia B)
    • 53. HEMOPHILIA-Tx  Prophylaxis  Preventive F VIII infusions  2 to 3x, weekly  To achieve F VIII level >1%  Expensive  Initiate after 1st joint bleed  Do not start before 6 months of age – increases risk of inhibitor devlpt
    • 54. HEMOPHILIA TREATMENT in the pipe line GENE THERAPY
    • 55.  NEXT PATIENT please…
    • 56. 13 / female Cc: menometrorhagia  Easy bruising and occasional epistaxis since childhood  Gum bleeding on toothbrushing  No previous BT  Iron supplement in the past
    • 57.  Family History  Maternal grandmother and mother with epistaxis and heavy menses  3 brothers and 2 sisters normal
    • 58.  Hb 114  Platelet 300 (150 – 450)  PT : normal; 12.9 sec INR 1.1  PTT : normal; 32.5 (23.5 – 33.5)
    • 59. ↑ PTT, TT Normal PT, platelet All normal Platelet dec Heparin VWD Platelet fxn d/o Mild factor def (VIII, IX, XI, XIII ) Collagen Disorder Vitamin C def CAMT, TAR,BSS WAS, GPS ITP 2 Infection
    • 60.  VIII  0.48 u /ml (0.5 – 1.5 u/ml)  VWF Ag  0.20 u /ml (0.5 – 1.5 u/ml)
    • 61. VonWillebrand Disease, type 1 DIAGNOSIS
    • 62. Von Willebrand Disease  Most common inherited bleeding disorder (Prevalence: 1% - by lab def’n; only 10% symptomatic)  Quantitative or Qualitative deficiency of vWF  Easy bruising / epistaxis from childhood / menorrhagia Dr. Erik Von Willebrand, 1926
    • 63. Diagnosis  Criteria  VWF Ag < 30%  Or VWF Ag 30-50% , in patient with clinical symptoms supportive of VWF
    • 64. The Von Willebrand Factor  Protein in plasma  Function 1. Tethers platelets to damaged endothelium 2. Binds and protects Factor VIII Endothelial cells w/stored VWF
    • 65. vWD
    • 66. vWD- Classification  Type 1  Classic ; 80% of patients  Partial quantitative deficiency  Type 2  Dysfunctional VWF- qualitative  Type 3  Nearly COMPLETE deficiency
    • 67. vWD-Inheritance  Mostly AD ; can be AR  Theoretically, equal males and females  But more females dxd (menorrhagia)  Can be acquired  rare  Hypothyroidism, Wilms tumor, Cardiac disease, Renal disease or SLE / Valproic acid  Most often caused by Ab to VWF
    • 68. vWD- S/Sx  Increased bruising and excessive epistaxis  Prolonged bleeding with trauma or surgery  Menorrhagia  Significant menorrhagia from menarche  prompt investigation for congenital bleeding d/o
    • 69. vWD-Labs  Initial screen: - PT normal - PTT sometimes prolonged > in type 3 (factor VIII dec) - Platelet sometimes dec > in types 2 and 3  Most of the time: PT, PTT, platelet --- NORMAL  Blood type ‘O’ – normally lower vWF
    • 70. VWD  Bleeding time - prolonged  Platelet function analyzer – prolonged closure time  vWF assay - Definitive test
    • 71. vWD -Treatment  VWD types 1 and 2  Desmopressin  Releases vWF from endothelial stores  IV or intranasal ( high concentration spray )  Variable response  measure VIII and vWF 60 minutes after  May cause fluid shifts (hyponatremia seizures )  Tachyphylaxis occurs (stored VWF limited)  Further therapy with VWF concentrate or cryoprecipitate
    • 72. VWD -treatment  Intermediate purity F VIII concentrates  Cryoprecipitate
    • 73. AdjunctiveTreatment  Antifibrinolytic agents (Tranexamic acid / E-aminocaproic acid )  Prevents plasminogen  plasmin  For mucosal bleeding  Topical thrombin and fibrin glue  Estrogen containing contraceptive tx  For menorrhagia
    • 74. Rare Coagulation Disorders
    • 75. Rare coagulation disorders  Other congenital coagulation factor deficiencies  Afibrinogenemia /hypofibrinogenemia  Deficiencies of factor V, VII, X, XI, XIII  Combined, occur in 1-500,000 to 1:2,000,000  Autosomal recessive  Most common : Factor VII def  Causes most bleeding sxs: Factor X and Factor XIII def
    • 76. Rare coagulation disorders  S/Sx  Umbilical stump bleeding  Delayed cord separation  Intracranial or intestinal hemorrhage  Muscle hematomas  Easy bruising  Prolonged bleeding ff heelprick
    • 77. Inherited platelet Disorders
    • 78. Inherited platelet disorders  Decreased number and abn function  Bernard Soulier Syndrome (BSS)  Wiskott Aldrich Syndrome (WAS)  Gray Platelet Syndrome (GPS)  Normal number but abn function  Glanzman Thrombasthenia (GT)  Storage Pool Disorder (SPD)
    • 79. Dec # and abn platelet fxn Defect S/Sx Labs BSS No GPIb/IX plt receptor -> defective binding to VWF ARecessive Bruising/ bleeding from infancy Moderate thrombocytopenia Large platelets GPS Alpha granule deficiency Severe bruising bleeding from early age Mild thrombocytopenia Large gray/Agranular platelets
    • 80. GLANZMANN THROMBASTHENIA Defect S/Sx Labs Normal number Normal morph Platelet GP IIb/IIIA (fibrinogen receptor) – FAILS TO AGGREGATE ARecessive Severe spont’ mucosal bleeding Presents in infancy BT Flow cytometry Plt aggregation
    • 81. SUMMARY
    • 82. Summary  Hemostasis  3 stages  Vasoconstriction  Platelet phase  Coagulation phase  Congenital bleeding disorders  Hemophilia A, B  VWD  Rarer coagulation disorders  Inherited platelet disorders
    • 83. Summary  Suspect a congenital bleeding disorder  Symptoms presenting in early infancy/childhood  Similar symptoms in family members  Consanguinity  Most common disorders  Hemophilia  VWD
    • 84. Summary  Do coagulation screen  Deranged PTT only  Think…  Hemophilia – hemarthrosis/intramuscular bleed  VWD – bruising / petechiae, epistaxis  Platelet, PT, PTT all normal  Think…  VWD  Platelet function disorder  Mild coagulation disorders
    • 85. Hemophilia A or B (factor VIII /IX def) VWD (VWF def or abn) Inheritance X linked De novo (1/3) AD (few AR) S/Sx Easy bruisability Hemarthrosis Soft tissue bleed Menorrhagia Easy bruisability Epistaxis Menorrhagia Labs Prolonged PTT Normal plt, PT, PTT < Prolonged PTT (few) > Confirmatory test Factor VIII /IX assay VWF assay Treatment Desmopressin (for mild Hemophilia A) Recomb Factor VIII /IX Cryoprecipitate /FFP Desmopressin Intermediate purity FVIII Cryoprecipitate

    ×