ParisTrousseau platelets: a manifestation of Jacobsen syndrome

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Paris-Trousseau platelets a manifestation of
Jacobsen syndrome

• Interesting Case
• Shubnum Chaudhery
• 08-23-05

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Paris-Trousseau platelets a manifestation of
Jacobsen syndrome

• 47 of patients w/ Jacobsen syndrome are
  thrombocytopenic
• An inherited disorder characterized by mild
  hemorrhagic tendency associated with 11q23
  chromosome deletion
• Thrombocytopenia is due to dysmegakaryopoiesis w/
  formation of giant alpha-granules (fusion) during
  prolonged residence in the bone marrow (delayed
  release)

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Paris Trousseau Syndrome

• Isoummune thrombocytopenia
• Bleeding defect is due to a platelet problem
• low platelet count
• abnormal platelet function

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Paris Trousseau Syndrome

• Eval of Peripheral Blood-Mainly normal sized
  platelets w/ 10-15 of platelets containing
  giant, red staining alpha granules that arise
  from fusion of normal sized organelles
• Bone marrow has increased megakaryocytes w/ many
  micromegakaryocytes.
• Platelet life span is usually normal indicative
  of ineffective platelet production

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• Two major components to clotting
• 1. Platelets (primary hemostasis) initial
  platelet plug
• 2. Clotting factors (secondary hemostasis)

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Platelet Disorders

• Quantitative vs Qualitative
• MCC of platelet related bleeding is
  thrombocytopenia
• 1st step in investigative process of defect of
  primary hemostasis is platelet count eval of
  peripheral blood smear

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• Hereditary platelet disorders fall into 3 broad
  categories
• defects of adhesion-adhesion occurs when injury
  causes platelets to attach to lining of blood
  vessel begin 1st phase of clotting process
• defects of primary aggregation- after platelets
  initially begin to adhere to the wall of injured
  blood vessel, additional platelets are called to
  site of injury and aggregate to each other
• defects of secondary aggregation- granules inside
  the platelets function to store release
  specific proteins that help platelets aggregate
  at the site of blood vessel injury

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Platelet Aggregation

• Measured by turbidimetric methods
• when platelets aggregate, the opalescent
  suspension of platelet-rich plasma becomes
  clearer allows more light transmission. The
  extent of aggregation is determined by measuring
  the increase in light transmission

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Platelet Aggregation

• Primary wave - reversible form of platelet
  aggregation unaccompanied by thromboxane
  synthesis or release of intraplatelet ADP
• Secondary wave-release of intraplatelet ADP
  synthesis of thromboxane A2 from Arach
  Acidinitiating irreversible aggreg (platelets
  release granules)

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Platelet Aggregation

• The primary wave is observed when platelets
  adhere to one another in the presence of an
  agonist.
• The secondary wave is characterized as the
  aggregation that occurs after the platelets have
  been stimulated to secrete the substances
  contained in their organelles.
• (Epi, collagen, ADP, ACA, ristocetin)

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Aggregation is stimulated by release of platelet
granules (2 classes)

• Alpha Granules Primary secondary platelet
  aggregation
• Albumin Platelet adhesion
• Alpha-2 antiplasmin
• C1 esterase inhibitor
• Platelet Factor 4 (PF4)
• Low affinity PF4
• Beta thromboglobulin
• Platelet derived growth factor
• Fibrinogen
• Factor V
• Fibronectin
• vWF antigen
• Dense Bodies Provide energy source for
  platelets
• ATP Platelet adhesion
• ADP
• Serotonin
• Calcium
• Provide energy source for

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Our patients report

• PERIPHERAL SMEAR SHOW MODERATE THROMBOCYTOPENIA
  WITH
• FEW LARGE PLATELETS.
• RBC- NO SCHISTOCYTES SEEN. RARE NRBC
• PRIMARY AGGREGATION WITH EPINEPHRINE, COLLAGEN,
  ADP / ACA ARE SEEN, BUT SECONDARY WAVES ARE
  ABSENT.
• RESPONSE TO RISTOCETIN IS NORMAL. SIMILAR
  RESPONSE MAY BE SEEN in DEFECTS OF PLATELET
  RELEASE REACTION , AND DRUG EFFECT.
• H/O JACOBSEN'S SYNDROME NOTED . THRMBOCYTOPENIA
  AND
• PLATELET FUNCTION DEFECTS ARE REPORTED IN ABOVE
  SYNDROME.

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• 8/7 transfused 50ml PRBC over 2 hrs
• Scheduled modified norwood for 8/16
• RV directed connected to PA via conduit (goretex
  tubing) that creates circulation to lungs
• wanted plts 150,000 for surgery
• Anticipated ECMO post surgery

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ECMOExtracorporeal Membrane Oxygenation

• Modified cardiopulmonary bypass technique used
  for short term support for cardiac or respiratory
  failure
• Therapy usually provided from 3-10 days (Dx)
• Provides gas exchange independent of the
  patients lungs, allows heart to rest
• The amt of red cell, platelet, FFP support to
  maintian hematologic hemodynamic equilibrium
  varies by clinical situation

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• The usual indication for mechanical circulatory
  support with VA ECMO in pediatric cardiac
  patients is inadequate oxygen delivery.
• Typical causes include
• low cardiac output
• severe cyanosis
• severe hypoxemia from acute respiratory failure

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• ECMO
• Partial Heart lung bypass
• Venoarterial
• Extracorporeal Flow 30-80 of total cardiac
  output
• Cardiac effect Partial support
• Duration
• O2 consumption transported extracorporeally 20
  - 90
• CO2 consumption transported extracorporeally 20
  - 90
• Prevalence Most common route used in neonates

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• Blood drainage sites IVC
• Blood infusion sites Aortic root
• Technique of drainage Venous blood drained by
  gravity from a large bore cannula inserted into
  either the right internal jugular or the femoral
  vein advanced so that tip is in RA
• Technique of reinfusion After blood is passed via
  membrane lung, it is returned Adult axillary
  femoral artery Neonate Right common Carotid
• Distribution of oxygen decarbondioxide
  blood Non uniform ABGs likely. Dependent on tip
  of arterial cannula magnitude of extracorporeal
  flow

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• Advantage for neonates
• Total systemic flow is is a summation of cardiac
  output extracorporeal flows provides partial
  CPB support by decreasing preload native
  cardiac output.
• Provides cardiac support in severe pulmonary
  hypertension offers a wider safety net for
  hemodynamically labile patients
• It has been noted that the need for
  anticoagulation in ECMO leads to hemorrhage with
  subsequent use of blood products which results in
  blood loss consumption of rbcs, platelets,
  FFP.

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• Maintain platelet count 150,000 (justified based
  on clinical publications on intracranial
  hemorrhage)
• PRBC- watch K levels (washed in our case) days old
• FFP - adjust calcium levels
• Valued to achieve high hcts in early stage of
  support
• MAP 35-60 mmHg to reduce risk ICH
• Platelet transfusion - give irradiated, CMV neg,
  leukocyte reduced
• Expected mortality w/ conservative trtmnt should
  be 80

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ECMO

• Who runs-
• ECMO technician for machine
• Nurse for patient
• Check coag studies hourly prn to assess
• Heparin is administered through drip directly
  into circuit (check ACT hourly)
• Blood products are replaced until bleeding in
  under control
• Arterial filter-
• May exacerbate platelet consumption
• Traps air, thrombi other emboli
• In line bubble detector
• Detects microbubbles in arterial line and turns
  off pump

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Future of patient

• MCC of death and illness in Jacobsens is
  Congital Heart Defects bleeding
• Recent research shows that while most childrens
  platelet counts return to normal as they approach
  adolescence, the abnormal platelet function
  persists.
• Degree of platelet dysfunction is variable,
  ranging from being undetectable under normal
  circumstances, to causing life-threatening
  bleeding complications.