Platelet disorders in pregnancy
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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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Platelet disorders in pregnancy

Platelet Disorders in Pregnancy

Joe Dietrick, CRNA, M.A.

Have A Nice Day Anesthesia, LLC

Chillicothe, MO


Overview

Overview

  • Hemostatic process

  • Coagulation factors

  • Coagulation tests

  • Select platelet disorders

    • Von Willebrand Disease

    • Immune Thrombocytopenic Purpura

    • Thrombotic Thrombocytopenic Purpura


General hemostasis

General Hemostasis

Hemostasis


General hemostasis1

General hemostasis


Hemostasis

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


Platelet function 1

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


Platelet function activation 1

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


Coagulating backwards 2

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


Coagulation factors 2

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


Coagulation tests

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


Von willebrand disease 3

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


Von willebrand disease 31

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


  • Vw dz what to do 4

    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


    Vw dz treatment options 4

    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


    Vw dz ddavp 4

    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


    Vw dz factor replacement 4

    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


    Vw dz other products 4

    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


    Vw dz oh anesthesia

    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


    Nice case report 11

    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


  • Itp or atp auto immune thrombocytopenic purpura 6 7

    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


    Itp atp we all 6 7

    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


    Systematic review 2009 10

    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


    Systematic review 2009 101

    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


    Ttp thrombotic thrombocytopenia purpura 6 7

    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


    And all of this means

    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


    References

    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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