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Platelet Disorders in Pregnancy

Platelet Disorders in Pregnancy. Joe Dietrick, CRNA, M.A. Have A Nice Day Anesthesia, LLC Chillicothe, MO. Overview. Hemostatic process Coagulation factors Coagulation tests Select platelet disorders Von Willebrand Disease Immune Thrombocytopenic Purpura

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Platelet Disorders in Pregnancy

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  1. Platelet Disorders in Pregnancy Joe Dietrick, CRNA, M.A. Have A Nice Day Anesthesia, LLC Chillicothe, MO

  2. Overview • Hemostatic process • Coagulation factors • Coagulation tests • Select platelet disorders • Von Willebrand Disease • Immune Thrombocytopenic Purpura • Thrombotic Thrombocytopenic Purpura

  3. General Hemostasis Hemostasis

  4. General hemostasis

  5. Hemostasis • 3 initial events • Vascular spasm • Platelet plug • Clot formation (coagulation) • Goal: Fibrinogen  fibrin: meshwork • Fibrous tissue formation • Solidified fibrin mesh • Fibrinolysis • Normally a good thing

  6. Platelet function1 • 2 forms • Circulate as Inactive: disc • Won’t interact with normal vascular endothelium • Activated: sphere with projections • 4 functions of Activated PLTs • Adherence to collagen • Activation & secretion of other mediators • Aggregation • Interaction w/other coag factors Lesoine, J. Electron Microscopy of Human Blood Cells. Retrieved 04/20/2009 from http://www.optics.rochester.edu/workgroups/cml/opt307/spr06/john/lesoineTEMSEM.htm

  7. Platelet function: Activation1 • Occurs on exposure to collagen • Clump PLTs together to seal leak • Activated PLTs release… • ADP: PLT aggregation & activation • Thromboxane A2: ↑ ADP & vasconstriction • ASA inhibits TXA2 production • Activated PLTs exposes PF3 • Phospholipid platform for coagulation

  8. Coagulating – backwards2 • Goal: Fibrinogen  fibrin • Fibrin meshwork on the PLT plug • Requires thrombin • Prothrombin  thrombin • Initiation: exposure of phospholipid platform • Extrinsic: release of thromboplastin • Intrinsic: exposure of PF3 & collagen Common Pathway Lesoine, J. Electron Microscopy of Human Blood Cells. Retrieved 04/20/2009 from http://www.optics.rochester.edu/workgroups/cml/opt307/spr06/john/lesoineTEMSEM.htm

  9. Coagulation factors2 • Circulate as procoagulants (except Ca++) • Vit. K dependent (warfarin-inhibited) • 2 (prothrombin), 7,9,10 • Synthesized in liver (except vWF) • Increased activity of Factors 7-10 in pregnancy: decreased response to warfarin • Ca++ enhances many steps

  10. Clinical assessment is most important Understand what is & isn’t tested Common tests/pathways are aPTT intrinsic & common, heparin PT extrinsic & common, warfarin INR Other tests include: ACT intrinsic & common, heparin BT platelet function & vascular function Quantitative studies: PLT Fibrinogen FDP/D-dimer Coagulation tests

  11. von Willebrand Disease3 • Most common inherited bleeding disorder • VIII:vW (aka vWF) – abnormal  vW Dz • VIII:C (aka VIII) – deficient  hemophilia • PLT adhesion to collagen: “intercellular glue” • Ristocetin enhances rxn • Increases ½ life of F-VIII • Basic testsSymptoms Normal PLT count Mild bleeding & bruising Abnormal BT May be unaware of dz Platelet interactions. Retrieved from UpToDate Online, 04/22/09: http://www.uptodateonline.com/online/content/images/hema_pix/Platelet_interactions.jpg

  12. von Willebrand Disease3 • Subtypes • 1 quantitative (not enough) 70% • 2 qualitative (don’t work well) 25% • 4 variants of Type 2 • 3severe, with  F-VIII as well • Mid-late pregnancy:  vWF 2-3x normal • Type 2 qualitative problems – still a problem • Most don’t require treatment • PP hemorrhage:  vWF in PP period

  13. vW Dz: what to do4 • Consult hematologist • Lab tests (diagnostic) • F-VIII – normalvWF-dependent survival • vWF:Ag < 30 IU/dl quantitative • vWF:RCo < 30 IU/dl qualitative • NIH (2008) • High-risk OB referral for delivery • F-VIII or vWF:RCo < 50, or • h/o severe bleeding

  14. vW Dz: treatment options4 • F-VIII & vWF:RCo > 50 • Before delivery or procedure • Maintain for 3-5 days PP • How to achieve • DDAVP • Factor replacement (Humate, Alphanate) • Cryo • FFP • PLT • Anti-fibrinolytics

  15. vW Dz: DDAVP4 • Desmopressin; synthetic vasopressin/ADH • Effectiveness tested before needed • 3 – 5 fold increase • Tachyphylaxis • 0.3 µg/kg IV Q 12° • Peak effect 30 – 90’, duration 6 – 12° • Max 20 µg, dilute in 50 ml, give over 30’ • Hyponatremia (+ fluids & oxytocin) • Limited data for use in pregnancy

  16. vW Dz: Factor replacement4 • vWF & F-VIII, but not interchangeable • Purified products  ↓ infectious risk • Humate-P • Indication:DDAVP contraindicated or inadequate • FDA approved prophylactic for surgery • Alphanate SD/HT • Indication:DDAVP contraindicated or inadequate • Not for Type 3 undergoing major surgery

  17. vW Dz: Other products4 • Cryoprecipitate • vWF & F-VIII – 1 pool (6 bags) • Strongly discouraged except in life-threatening circumstances • Fresh Frozen Plasma • Platelets • 10-15% of blood vWF • Adjunct, not primary tx • Anti-fibrinolytics

  18. vW Dz: Oh, anesthesia • Pre-delivery anesthetic evaluation • Avoid NSAIDs • Regional • NIH (2008): “If… • VWF:RCo and FVIII levels can be monitored and maintained above 50 IU/dL during labor and delivery, and • no other coagulation defects are present, then • regional anesthesia may be considered. Grade C, level IV.”4 • vWF & F-VIII > 50  regional can be considered3

  19. Nice case report11 • 15 y/o ♀Type 1 vWDz: : ACL reconstruction • Prevanesth: severe N/V with FentPCA (?) • Epidural post-op pain management • Preop assessment • vWF-a 48%,vWF-Rco 42%, F-VIII 48% • DDAVP trial 2 wks prior  successful • DOS: thorough consent • DDAVP, levels > 150% prior to procedure • DDAVP on POD 1 & 2

  20. ITP or ATP:Auto-Immune Thrombocytopenic Purpura6,7 • Lab • ↓ PLT < 100k (quantitative) • Nl – ↑ megakaryocytes (in bone marrow) • Diff Dx numerous • IgG-antibody mediated PLT destruction • Attack glycoproteins on PLT surface • Can cross placenta, esp 3rd trimester • Petechiae; young healthy females • Mortality 2° intracranial hemorrhage • Theoretically, may also occur in fetus

  21. ITP, ATP, we all…6,7 • RX: PLT > 50k (OB) PLT > 80k (Anesth) • Corticosteroids • IV immunoglobins • Splenectomy (2nd trim) • Rhogam (anti-D), [Rh+ pts only] • OB Concerns • Delivery method based on indications • Neuraxial anesthesia based on PLT count • Avoid NSAIDs

  22. Systematic Review (2009)10 • vWD • 74 techniques, all labor analgesia • No complications in 72 LEA, 2 combined • 64: Nl vWD indices • 10: treatment initiated prior to procedure • Tx: DDAVP or concentrates

  23. Systematic Review (2009)10 • ATP • 326 techniques, 324 OB; • No complications in 283 Epid, 41 spinal • 3 cases • Dx by  PLT after LEA: 20k, 18k, 26k! • PLT < 50k  tx (generally) • Cath removal • 1 of 14 articles tracked • Attempted to have >60k • But… 5/135 < 50k @ removal

  24. TTP:Thrombotic Thrombocytopenia Purpura6,7 • Disseminated PLT aggregation •  vWF cleaving protease • 5 features • ↓ PLT  Hemolytic anemia • Renal failure  Fever  Neurologic signs • Tx: Plasmapheresis, steroids, prostacyclin • PLT transfusions historically avoided • 2009: don’t withhold if surgically/procedure indicated • Neuraxial anesthesia contraindicated6

  25. And all of this means… • vW Dz • Lab: factors > 50 • 1° treatment: DDAVP, ideally pre-tested • Type 3 won’t respond • ITP is quantitative deficiency • May be on steroids • May require splenectomy while pregnant • TTP is deadly • Uncomplicated PLT ≥ 80k safe, Epid/SAB9

  26. References • Petrovitch, C. (1992). Perioperative Evaluation of Coagulation. ASA Refresher Courses in Anesthesiology, 20: 169-189. • Stoelting, R. (1991). Pharmacology & Physiology in Anesthetic Practice. Philadelphia: J.B. Lippincott Co. • Treatment of von Willebrand’s Disease. Retrieved from UpToDate Online 04/22/09: http://uptodateonline.com/online/content/topic.do?topicKey=coagulat/9525. • The Diagnosis, Evaluation, & Management of von Willebrand Disease (2008). National Institutes of Health, Pub 08-5832. • Butwick, A. & Carvalho, B. (2007). Neuraxial anesthesia for cesarean delivery in a parturient with type 1 von Willebrand disease and scoliosis. Journal of Clinical Anesthesia 19: 230–233 • Sharma, S. & Lechner, R. (2004). Hematologic & Coagulation Disorders. In Chestnut, D. (Ed), Obstetric Anesthesia, Principles & Practice, 3rd Ed ( Pg 764- 779). • Strong, J. (2003). Bleeding disorders in pregnancy. Current Obstetrics & Gynaecology, 13:1-6. • Swisher, K. et al (2009). Clinical outcomes after platelet transfusions in patients with thrombotic thrombocytopenic purpura. TRANSFUSION, 49:873-887. • Joost, J et al. (2010). The risk of spinal haematoma following neuraxial anaesthesia or lumbar puncture in thrombocytopenic individuals. British Journal of Haematology, 148, 15–25. • Choi, S & Brull, R (2009). Neuraxial Techniques in Obstetric & Non-obstetric Patients with Common Bleeding Disorders. International Anesthesia Research Society, 109(2):648-660. • Hara, K et al (2009). Considerations for epidural anesthesia in a patient with type 1 von Willebrand disease. Journal of Anesthesia, 23:597-600.

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