QUALITATIVE DISORDERS: PLATELETS &

VESSELS

BLEEDING
 SUPERFICIAL bleeding- Associated with platelet defect or vascular
disorder
 Petechiae – bleeding of small blood vessel
 Gingival bleeding
 Epistaxis
 DEEP tissue bleeding- Associated with plasma clotting factor deficiencies
 Hematoma or hemarthrosis

COAGULATION PLATELET/
DISORDER VASCULAR
DISORDER
SITE OF BLEEDING DEEP TISSUE SKIN, MUCOUS
MEMBRANES
PETECHIAE RARE COMMON
ECCHYMOSIS LARGE, DEEP SMALL, SUPERFICIAL
DEEP DISSECTING COMMON RARE
HEMATOMAS
HEMARTHROSIS COMMON RARE
DELAYED COMMON RARE
BLEEDING
BLEEDING AFTER YES NO
CUTS & SCRATCHES
BLEEDING AFTER IMMEDIATE, MILD DELAYED 1-2 DAYS,
SURGERY OR SEVERE
TRAUMA

QUALITATIVE PLATELET DISORDER

 A problem with the structure or function of the platelet
 The disorder results in a poor “quality” of clotting
 Common causes include
 Missing or defective proteins on the surface of the platelet membrane
  A deficiency or abnormality in the platelet granules or their contents
(also known as a “storage pool disorder”)

DISORDERS OF PLATELET SECRETION (RELEASE

REACTIONS)
 STORAGE POOL DISEASE
 DENSE GRANULES DEFICIENCIES
-Disorder arises from an inability to package the dense granule
content.
-Serotonin transport mechanism disorder
-Nucleotide transporter MRP4 (ABCC4) gene disorder
 ALPHA GRANULE DEFICIENCIES
- Alpha granules are storage for proteins
- 50-80 alpha granule per platelet, responsible for the granular
appearance in PBS
 THROMBOXANE PATHWAY DISORDERS
 Aspirin like effects
 DENSE GRANULE DEFICIENCIES
Hermansky-Pudlak Syndrome
 Chediak-Higashi Syndrome
Wiskott-Aldrich Syndrome
Thrombocytopenia- Absent Radius (TAR) Syndrome

 ALPHA GRANULE DEFICIENCY

Gray Platelet Syndrome
 Hermansky - Pudlak syndrome (HPS)
 Autosomal Recessive, HPS-1 gene (Chromosome 10q23)
HPS-1 gene – production and control of melanosome, dense granules,
lysosomes
 Tyrosine (+)
Severe oculocutaneous albinism associated with photophobia, rotary
nystagmus, and loss of visual acuity
Excess accumulation of ceroid - like material in RE cell
Mild to moderate bleeding diathesis
Platelet Factor is the major cause of death
 PT & APTT: Normal
Normal – Prolonged: bleeding time
Platelet Aggregation Standard: planted response in by basic course
 Chediak-Higashi Syndrome
Autosomal Recessive (1q)
Partial albinism - caused by abnormal large melanosomes
Large intracytoplasmic granules in WBC and platelets
Immune dysfunction- poor mobilization of marrow leukocyte pool,
defective chemotaxis and bacterial degradation activity
May lead to overwhelming infection or lymphoproliferative disorders
 Wiskott-Aldrich syndrome
X-linked recessive
Defective WASp- cytoskeletal reorganization
T cell reduces by age
LOW IgM, cell surface GP reduced
 Inability to mound an IgM response to the capsular polysaccharide of
bacteria
Recurrent pyogenic infections, eczema and bleeding caused by
thrombocytopenia
Gene alterations interfere with migration of WBC to the inflammation site
 Abnormal cell morphology & defective cytoskeleton dependent activation
signals
Abnormal cell to cell adhesion
IgA & IgE = elevated
IgG = normal
IgM = low
Decreased aggregation response to ATP epinephrine, & collagen
Low dense granules
 TAR syndrome
Autosomal Recessive
Thrombocytopenia (absence or hypoplasia of megakaryocytes) that
presents in early infancy with bilateral radial anomalies.
Skeletal abnormalities of the ulna, radius and lower extremities
Thumbs are present
Reduced number of platelets = hypomegakaryocytic thrombocytopenia
 Gray Platelet syndrome
Heterogenous disorder associated with abnormalities in alpha granule
formation and maturation
Autosomal recessive
Platelet inability to store alpha granule protein
Platelets appear gray on PBS
Mild thrombocytopenia, mild to moderate bleeding
Splenomegaly and fibrosis
 Easy bruising, menorrhagia, excessive postpartum or postoperative
bleeding
Platelet: normal with variable morphology
Platelet Aggregation Standard: normal in primary wave BUT absence in
secondary wave when simulated with ADP, epinephrine, & arachidonic acid
Resistin Agglutination: Normal
 Quebec Platelet defect
Autosomal dominant
 Delayed bleeding
Deficiency of alpha granule multimerin leading to decreased content of
platelet Factor V
Abnormal proteolysis of alpha granule proteins due to increased levels of
platelet urinary type plasminogen activator
Normal or Slight thrombocytopenia
 Reduced aggregation with epinephrine

SUMMARY

 Platelet Adhesion Disorder

 Von Willebrand Disease
 Bernard Soulier syndrome
 Platelet Aggregation Disorder
 Glanzmann thrombasthenia
 Congenital afibrinogenemia
 Disorder of Platelet Secretion & Abnormalities of Granules
 Storage pool deficiency
 Quebec platelet disorder
 Disorder of Platelet Secretion & Signal Transduction
 Defects in plt-agonist interaction
 Cytoskeletal Regulation Defect
 Wiskott-Aldrich syndrome (WAS)
 Membrane Phospholipid Defect
 Scott syndrome