Platelets And Vasculature. Hemostasis Week 12

Giant platelet syndrome
Defect – glycoprotein Ib/IX/V complex is missing

Heterozygotes – near normal platelets
Homozygous – moderate to severe bleeding, prolonged bleeding time, enlarged platelets, thrombocytopenia and decreased platelet survival, plt# 40,000/mcL to normal

Rare – autosomal recessive
Manifested in infancy
Defective platelet function ; ecchymoses, epistaxis and gingival bleeding

Aggregation studies – normal aggregation response to ADP, epinephrine, collagen and arachidonic acid
Do not respond to ristocetin and diminished response to thrombi
Lack of binding to VWF

Abnormality cannot be corrected by addition of human plasma or cryoprecipitate
Treatment of choice is platelet transfusions (apheresis platelets preffered to prevent alloantibodies), desmopressin acteate (DDAVP) and recombinant factor VIIa

Heterozygous are normal
Homozygous have serious bleeding problems
Seen in neonatal periods of life after circumcision
Clinical features – manifests as petechiae, purpura, menorrhagia, GI bleeding and hematuria

Abnormal or deficient in GP IIb/IIIa complex needed for binding fibrinogen, VWF, fibronectin
Leads to defect in hemostatic plug formation and serious bleeding

CBC is normal unless there is another underlying reason
Platelet factor 3 test is diminished because:
Fewer microvesicles
Complex GPIIb/IIIa missing for prothrombin
Not as activated by thrombin as normal platelets

Clinical features
Hemorrhage severe and disabling
Epistaxis, ecchymosis, hemarthrosis, subcutaneous hematoma, menorrhagia and GI and urinary tract hemorrhage

Treatment
Single donor platelet apheresis products, HLA-matched donor platelets, or ABO matched donor platelets
Hormonal therapy to control menorrhagia
Antifibrinolytic therapy to control gingival hemorrhage
Recombinant factor VIIa

Mucocutaneous hemorrhage and hematuria, epistaxis and easy and spontaneous bleeding
Platelet count is normal
Bleeding time usually prolonged
Platelet aggregation abnormalities usuallly seen

Most common plt secretion disorder
Dense granule deficiencies
Alpha granule deficiencies

Storage pool release reaction diseases

Thromboxane pathway disorders

Albinism, Nonalbinism. bleeding is mild limited to easy bruisability

Autosomal recessive
Tyrosinase positive oculocutaneous albinism
Mutations mapped to chromosome 19
Common abnormality in this disorder is marked dilation and tortuosity of surface-connecting tubular system (Swiss cheese platelet)

Rare autosomal recessive
Partial oculocutaneous albinism
Frequent pyogenic bacterial infection
Large lysosomal granules
Platelet δ-granule deficiency

Hermansky-Pudlak syndrome, Chédiak-Higashi syndrome

Unable to make antipolysaccaride antibodies which results in propensity for pneumococcal sepsis
Found primarily in males
Milder form – hereditary X-linked thrombocytopenia

Gene codes for 502 amino-acid protein, WASP found exclusively in hematopoetic cells
Platelets are structurally abnormal
δ granules are decreased, platelets are small
Decreased aggregation response to ADP collagen and epinepherine

Rare autosomal recessive disorder
Congenital absence of radial bones
Numerous cardiac and skeletal disorders
Thrombocytopenia
Platelets have structural defect in δ granules with abnormal aggregation response

Alpha granules are storage sites for proteins produced by the megakaryocyte (e.g. platelet-derived growth factor, thrombospondin, and platelet factor 4) or present in plasma and taken up by the platelets and transported to α-granules for storage (e.g. albumin, immunoglobulin G(IgG), and fibrinogen)

absence of the α granules
autosomal recessive. lifelong bleeding mild bleeding tendencies, prolonged bleeding time, moderate thrombocytopenia, fibrosis of the marrow and large gray platelets on Wright stained film

Electron photomicrographs appear to have no α granules
Contain vacuoles and small α granule precursors that stain positive for VWF and fibrinogen
Plasma levels of PF4 and α thromboglobulin are increased
Early onset of myelofibrosis

Deficient α and δ granules
Autosomal dominant inheritance
Membrane abnormalities

Autosomal dominant disorder
Deficiency of multimerin and shows protease related degradation of many α-granule structure

the pathway is required for mobilization of ionic calcium and initiation of events resulting in release in secretion and aggregation of platelets

inhibits cyclooxygenase an enzyme required in the release of thromboxane A2

required for storage secretion and platelet aggregation in response to epinephrine, ADP and low concentration of collagen

Clinical features – lifelong mild bleeding disorder
Laboratory features – lack aggregation response

Clinical features – mild bleeding
Laboratory features – failed adhesion with collagen

Drugs that are Inhibitors of

Inhibitors of Membrane Function

Cause of dysfunction coating of platelet membrane by paraprotein
Paraprotein interferes with fibrin polymerization
Hyperviscositysyndrome
Complications of amyloidosis
Clinical features – significant bleeding

Clinical and laboratory features –surgical bleeding after surgery, thrombocytopenia, severe platelet function defect

Reduction in clotting proteins, reduction of proteins in the natural anticoagulant pathways, dysfibrinogenemia and excessive fibrinolysis
Thombocythemia in association with hypersplenism and alcohol toxicity

Bleeding due to platelet dysfunction, concentration of guandinosuccinic acid is higher
causes prolonged bleeding time

Incidence seen in more than 150 families
Clinical features - platelets do not exhibit normal function
Laboratory features – prolonged bleeding time, platelet aggregation test results are abnormal, platelet function abnormality

Associated disorders – hyperlipidemia, diabettis mellitus, peripheral arterial occlusive disease, acute arterial occlusion, MI and stroke
Laboratory features – platelets aggregate at lower concentration of of aggregating agents
Spontaneous aggregation
Spontaneous pool disease – exhausted platelets

Autosomal dominant. Thin walled blood vessels w/ discontinuous endothelium, inadequate smooth muscle and discontinuous endothelium, inadequate elastin. Telangiectasis – dilated superficial blood vessels that create small focal red lesions . Epistaxis, skin and mucous lesions, Bleeding time normal

Giant cavernous hemangioma (vascular tumor)
Thrombocytopenia
Bleeding diathesis
Acute or Chronic DIC, intravascular coagulation and microangiopathic hemolytic anemia

autosomal dominant, recessive or X-linked
Hyperextensible skin, hypermobile joints
Positive tourniquet and prolonged bleeding

Autoimmune disease – mediated by immune complexes that contain IgA
Clinical features – disease of children 3-7 years old
Laboratory features – platelet count is normal
WBC and ESR is elevated

platelet function inhibited by myeloma proteins.
Clinical features – cause severe hemorrhagic manifestations due to hyperviscosity and platelet dysfunction. abnormality in platelet aggregation, secretion, clot retraction, and procoagulant activity
Treatment – plasmapheresis and chemotherapy

the deposition of abnormal quantities of amyloid in tissues. Amyloid is fibrous protein consisting of rigid, linear, non-branching, aggregated fibrils
Clinical features – purpura, hemorrhage, thrombosis. abnormal platelet function and thrombocytopenia
Treatment – none effective

more common in elderly men
Vascular abnormality – lack of collagen support for small blood vessels and loss of subcutaneous fat and elastic fibers
Clinical features – dark blotches, age spots
Laboratory features – lab tests normal and no bleeding manifestations

Inducing drugs – aspirin, barbituates, diuretics, digoxin, methyldopa
Clinical features – petechiae, antibodies to vessel wall components,

Miscellaneous causes of vascular purpura

what does warfarin do?

Specimen collection tubes

Ratio of blood to anticoagulant

Rules of collection

Hemostasis collection errors that require collection of a new specimen

Collecting from indwelling catheters

needle gauge for 25 mL specimens

needle gauge for >25 mL specimens

needle gauge for pediatric use

EDTA is used for

heparinized anticoagulant is used for

CTAD blue stopper used for

Storage times
Prothrombin time (PT)

Storage times. Activated partial thromboplastin time (APTT)

Storage requirements
Platelet aggregometry studies

Light-transmittance optical aggregometers use

Clot-based plasma testing use

Can be stored frozen at

platelet function tests

bleeding time

Disorders with prolonged bleeding time

Problems with bleeding time test

Platelet adhesion, aggregation, and secretion are assesed by

Process of aggregation requires

PRP aggregometry uses

Platelet processes measured –simultaneous measurement of platelet aggregation and secretion of adenosine triphosphate from activated platelet δ granules

platelet agonists, platelet aggregometry

Normal results – normal concentration of functional VWF and platelets possess a functional VWF receptor, GP Ib/V/IX
Abnormal results except for subtype 2B VW produce a reduced or absent reaction although alll other agonists generate normal tracings

conditions detected from platelet lumiaggregometry

conditions detected from platelet lumiaggregometry