HEMA 2 - PLATELET DISORDERS Flashcards
platelets are produced predominantly by the ______ as a result of budding of the _____
Bone Marrow Megakaryocytes ; Cytoplasmic Membrane
Megakaryocytes are derived from the _______, which is stimulated to differentiate to mature megakaryocytes under the influence of various cytokines including ___________.
Hemopoietic Stem Cells ; Thrombopoietin
disorders of platelet adhesion - deficiency of glycoprotein Ib/IX
bernard-soulier syndrome
disorders of platelet aggregation - deficiency of glycoprotein IIb/IIIa
glanzmann-thrombasthenia
disorders of platelet secretion
alpha or dense granules deficiency
platelets fail to promote activation of the blood clotting proteins
disorders of platelet procoagulant activity
acquired platelet function disorders, drug like …
drugs like aspirin, non-steroidal anti-inflammatory drugs like indomethacin, ibuprofen.
congenital abnormalities of platelets can be divided into _________ and those of _________
disorders of platelet production ; platelet function
congenital abnormalities all are very _____
rare
In general they cause moderate to severe bleeding problems.
Congenital abnormalities
- an autosomal recessive preleukemic condition which often presents as thrombocytopenia with skeletal or genitourinary abnormalities.
Fanconi’s Anemia
Congenital abnormalities lab features
- Abnormal chromosomal fragility.
- The condition can be cured with bone marrow transplantation (BMT)
rule out pseudotrhombocytopenia
- sequestration
- production
- destruction
look for splenomegaly
sequestration
causes of splenomegaly (sequestration)
- infection
- inflammation
- congestion
- malignancy
- red cell disorders
- storage disorders
bone marrow investigation review meds
production
included in production - bone marrow investigation review meds
- aplasia
- infiltration
- ineffective megakaryopoiesis (e.g MDS)
- selective impairment of platelet production
look for underlying disorders review meds
destruction
included in destruction - bone marrow investigation review meds
- immune auto-immune (ITP, SLE) rugs infection allo-immune
- none-immune seosis DIC, TTP, HUs hypertensive disorders of pregnancy
also included in approach to thrombocytopenia
artefactual (false) or pseudothrombocytopenia and congenital thrombocytopenia
clot in the sample and platelets clumped
artefactual (false) or pseudothrombocytopenia
rare inherited disorders (e.g may hegglin anomaly)
Congenital Thrombocytopenia
platelet count is less than 100,00 cu mm =
thrombocytopenia
Platelet count <50,000
variable risk
Platelet count <20,000
transfusion appropriate
Platelet count <10,000
spontaneous hemorrhage
mucus membrane bleeding =
platelet dysfunction
platelet dysfunction includes
Epistaxis
Gingival
Vaginal Bleeding
Petechiae
Purpura
a type of von Willebrand disease that is qualitative alterations in the vWF structure and function
Type 2
a type of von Willebrand disease that is least common and most severe
Type 3
complete absence of vWF in plasma or storage organelle is a type ___ vWD
Type 3
acquired vWD inclues
- lymphoproliferative disease
- tumors
- autoimmune disease
- cardiac/valvular disease
- medications such as valproic acid
- hypothyroidism
platelet morphology: giant platelets includes
- May Hegglin Anomaly
- Bernard-Soulier Syndrome
- Alport Syndrome
- Storage Pool Syndrome
- normal total platelet mass
- normal platelet number in circulation
Pseudothrombocytopenia
causes of pseudothrombocytopenia
- inadequate anticoagulated blood sample
- EDTA-induced platelet clumping
- Giant platelet
- Platelet satellitism
Associated with decreased or ineffective megakaryopoiesis and thrombopoiesis.
Decreased Platelet Production
decreased platelet production marrow damage includes
o Aplastic Anemia
o Fanconi’s Anemia (defect in DNA repair genes)
o Malignancy (with or without myelophthisis)
decreased platelet production also deals with
- Congenital Defects (congenital thrombocytopenia)
- Paroxysmal Nocturnal Hemoglobinuria (PNH)
decreased platelet production also deals with viral infections such as
o Rubella, CMV, EBV, HIV & Hep-C
decreased platelet production also deals with ineffective production such as
o Nutritional Deficiencies such as B12, Folate, Severe Fe deficiency.
decreased platelet production also deals with drugs such as
o Thiazides, Estrogen, Chemotherapy, Linezolid
decreased platelet production also deals with toxins such as
o Alcohol, Cocaine
decreased platelet production also deals with marrow failure (pancytopenia) such as
o Aplastic Anemia, Chemotherapy, Toxins
decreased platelet production also deals with B-12, Folate or _____ deficiency
Iron
decreased platelet production also deals with drugs that can selectively reduce platelet production such as
o Alcohol
o Estrogens
o Thiazides
o Chlorpropamide
o Interferon
decreased platelet production also deals with Amegakaryocytic Thrombocytopenia such as
o Myelodysplasia (pre-leukemia)
o Immune (related to aplastic anemia)
decreased platelet production also deals with ______ and ________ thrombocytopenia
- Cystic thrombocytopenia (rare)
- Inherited thrombocytopenia
TTP is a short term for
THROMBOTIC THROMBOCYTOPENIC PURPURA
TTP is characterized by __________ and ________________.
microangiopathic hemolytic anemia ; profound intravascular platelet clumping
Evaluation of suspected hereditary and acquired disorders of platelet function.
PLATELET AGGREGATION TESTING
Platelets normally contain three major types of granules
- alpha granules
- dense granules
- lambda granules
granule that contains fibrinogen, PF4, Factor V, Von Willebrand Factor.
Alpha Granules
granule that contains ADP or ATP, calcium and serotonin
Dense Granules
a granule that is similar to lysosomes and contain several hydrolytic enzymes.
o Lambda Granules
Hereditary platelet function disorders includes
o Rare defects of adhesion = Bernard Soulier Syndrome
o Rare defects of aggregation = Glanzmann Thrombasthenia
o More common defects of secretion = Alpha or Dense Granule Deficiency, Aspirin-like Defects, or Other primary defects.
Bernard Soulier Syndrome is a rare defects of _____
adhesion
Glanzmann Thrombasthenia is a rare defects of _____
aggregation
Alpha or Dense Granule Deficiency, Aspirin-like Defects, or Other primary defects is a more common defects of _______
secretion
Acquired platelet function disorders are more common than the _________ and include _________.
hereditary disorders ; drug-induced platelet dysfunction
drug-induced platelet dysfunction includes
o Aspirin
o NSAID’s
o Clopidogrel
o Antibiotics
o Various cardiovascular
o Psychotropic Drugs
o Uremia
o Myeloproliferative disorders
TREATMENT OF PLATELET DISORDERS (Congenital Disorders)
- Platelet Transfusion = Leucodepleted, HLA compatible and Irradiated
- DDAVP
- Tranexamic Acid
- Recombinant factor VIIa
- Bone Marrow Transplantation
