ACQUIRED DEFECTS OF PLATELET FUNCTION  Cardiopulmonary Bypass Surgery

1. Drug-Induced defects  Liver disease

 Drugs that inhibits prostaglandin pathway  Chronic alcoholic cirrhosis
 Aspirin and other drugs that inhibit prostaglandin  Upper Gl bleeding
synthesis (within 7 days STOP testing)  Uremia
 Chronic alcohol consumption  Hereditary Afibrinogeniemia
 The impaired platelet function seems to be related 3. Hyperaggregable platelets
at least in part to inhibition of thromboxane QUALITATIVE VASCULAR DISORDERS
synthesis DISORDERS AFFECTING THE VESSEL WALL
 3 days NO ALCOHOL INTAKE
 Drugs that inhibit membrane function 1. Henoch-Schonlein Purpura
 (P2Y12) ADP receptor inhibitor  Acquired condition
 Steady state is reached 3-5 days  “Classic” Clinical Tetrad
 P2Y12 inhibitors is binding to the platelet  Allergic purpura/ anaphylactoid purpura
membrane STD receptors for ADP and the  Normal: Platelet, Coagulation Test, and Bleeding time
prevention of ADP binding to those receptors.  Increased: WBC count, and ESR
 GPIIB/Illa receptor inhibitor  Severe condition, anemia is possible
 Interference with the ability of this receptor to bind Henoch-Schonlein Purpura
fibrinogen inhibits platelet aggregation stimulated in  Small-vessel vasculitis
 Deposition of IgA in skin, mucous membranes, kidney,
response to all of the usual platelet aggregating
abdominal vessels
agents.  Most common vasculitis in childhood (2-11 yr)
 White/Asian men >>>everyone else
2. Disorders that affect platelet function  Typically preceded by a URI
 95% full recovery after 3-4wks
Antiplatelet Agents
 Adult symptoms typically worse
Drug Mechanism of Action  Renal failure rare but possible
Therapeutic Antiplatelet Agents o 5-15% in children
Aspirin Irreversible inhibition of COX1 o 30-50% in adults
Naproxen Reversible inhibition of COX1
Sulfinpyrazone Reversible inhibition of COX1 2. Hereditary Hemorrhagic Telangiectasia
Ibuprofen (and Reversible inhibition of COX1
 AKA Rendu-Osler-Weber Syndrome
related)
 Telangiectasia– dilated superficial blood vessels that creates
Clopidogrel Irreversible inhibition of
P2Y12 receptors
small or coccal red lesion. Occurred throughout the body BUT
Prasugrel Irreversible inhibition of
most obvious in the face, lips, tongue, conjunctiva, nasal mucosa,
receptors P2Y12 receptors fingers, toes, trunk.
Ticagrelor Reversible inhibition of P2Y12  Characterized by thin-walled blood vessels with a discontinuous
receptors receptors endothelium, inadequate smooth muscle and elastin in the
Abciximab Inhibition of GP IIb/IIIa (aIIb/B3) surrounding stroma
Eptifibatide Inhibition of GP IIb/IIIa (aIIb/B3)  Patients do well despite lack of specific therapy
Tirofiban Inhibition of GP IIb/IIIa (aIIb/B3) Criteria
Dipyridamole Inhibition of PDE (and Epistaxis Spontaneous and recurrent
cAMP breakdown) Telangiectasa Multiple, at characteristic sites: lips, oral
Aggrenox Inhibition of COX1 and PDE cavity, fingers, and nose
Drugs with Antiplatelet Effects Visceral lesions Such as gastrointestinal telangiectasia, or
Alcohol Inhibition of thromboxane synthesis pulmonary, hepatic, cerebra, or
(?) spinal AVMs
Nitrofurantoin Unknown Family history A first-degree relative with HHT
Dextrans Interference with membrane function according to these criteria
Hydroxyethyl Interference with membrane function HHT diagnosis is
(HETA) starch Definite If three or more criteria are present
Possible or If two criteria are present
 Myeloproliferative Neoplasms suspected
 PCV Unlikely If fewer than two criteria are present
 CML Abbreviations: AVM, arteriovenous malformations; HHT;
 ET hereditary hemorrhagic telangiectasia.
 MMM
 Multiple Myeloma and Waldenstrom
Macroglobulinemia – results from putting platelet
membranes by paraprotein & does not depend on the
type of paraprotein presence. I addition interacting to
plt the paraprotein may interfere with fibrin
polymerization and function of other coagulation
protein
 5. Paraproteinemia
 Abnormality in platelet aggregation, secretion and
procoagulant activity
 Acquired condition
 Plasma paraprotein and are likely due to coating of the
platelet membrane with the paraprotein. Inhibiting
adhesion and activation clotting factors on platelet
surfaces.
 Abnormal results of: PT, aPTT, Thrombin Time, Bleeding Time
 Monoclonal Immunoglobin/Immunoglobulin light chain in
the blood or urine – resulting from clonal proliferation of
plasma cells/ B cells
 3 major disorders associated with Paraproteinemia
 MGUS/Monoclonal Gammopathy of
Undetermined Significance
 MM/Multiple Myeloma
 Waldenstrom
3. Hemangioma Thrombocytopenia Syndrome
 AKA” (Kasabach-Merritt Syndrome)
 Inherited condition
 Associated with acute or chronic DIC, and
microangiopathic hemolytic anemia.
 Giant cavernous hemangioma (vascular tumor) leading
to thrombocytopenia
 Bleeding diathesis
 Infants, women 6. Senile Purpura
4. Ehlers-Danlos Syndrome  Acquired condition
 Inherited autosomal dominant, recessive or x linked trait.  occurs more commonly in elderly men than in women
 Manifested by hyperextensible skin, hypermobile  lack of collagen support for small blood vessels and loss
joints, joint laxity, fragile tissues, and a bleeding of subcutaneous fat and elastic fibers.
tendency, primarily subcutaneous hematoma  No bleeding
formation.  BT, CT, Platelet count and clot retraction time normal
 Increased capillary resistance test

7. Amyloidosis
 The deposition of abnormal quantities of amyloid in tissues,
may be primary or secondary and localized or systemic
 Fibrous protein consisting of rigid, linear non- branching
aggregated fibrils approx. 7.5 – 10 nn wide & indefinite length
 Purpura
 Hemorrhage
 Thrombosis
 TYPES:  Abnormal platelet function and sometimes
 Gravis-EDS classical features thrombocytopenia is observed
 Mitis- Mild expression of classical EDS
 Hypermobile- Marked joint laxity 8. Drug Induced Vascular purpuras
 Vascular-Severe life-threatening  Mechanism includes development of antibody vessel wall
vascular hemorrhage component & development of immune complexes & changes
 X-linked-features similar to type Il (different vessel wall permeability
inheritance)  Aspirin, warfarin, barbiturates, diuretics, digoxin, methyldopa,
 Ocular/Scoliosis- eye problem and several antibiotics
 Arthrochalasis- Joint hyperlaxity and  Sulfonamides and iodides have been implicated most
congenital dislocations frequently
 Periodontal- Dental problems and classical EDS  Few petechiae to massive petechial eruptions may vary
Villefranche Berlin Protein Gene  Tx: discontinue drug
classification Classificatio Abnormality abnormalit
n y
Classical EDS type I/II Type V collagen COL5A1
9. Others/Miscellaneous
,  Scurvy
COL5A2  Insufficient dietary intake of vitamin C (ascorbic acid)
Hypermobility EDS type III Unknown Unknown
Vascular EDS type IV Type III collagen CO3A1  Characterized defective synthesis of collagen &
Kyphoscoliosis EDS type VI Lysyl PLOD1 hyaluronic acid
hydroxylase
deficiency
 Symptoms: bleeding of the skin & mucus, gingivitis, rough
Arthrochalasia EDS type Type I collagen COL1A1, / dry skin, joint & body ache, fatigue, depression,
VIIA/B COL2A2
Dermatosparaxi EDS type N-proteinase ADAMST2
susceptible to infection, muscle weakness
s VIIC
EDS: Ehlers-Danlos syndrome
10. Ecchymoses
 superficial, bleeding is usually mild, and
laboratory test results are most often normal