Week 24 - Bleeding Disorders & Malignancy Flashcards
What cell produces platelets?
Megakaryocytes
What proportion of platelets are trapped in the spleen?
1/3 usually.
Describe how platelets function.
Primary function
- adhesion to vessel wall (Gp1a2a on platelets snag exposed collagen, Gp1b9 on platelet binds VWF… platelets become more spherical and extrude pseudopods), secretion of granule contents (collagen exposure activates arachidonic acid synthesis, forms thromboxane A2, activates PLC, increases Ca, releases granules), aggregation (Gp1b9 binding activates Gp2b3a, allowing fibrinogen to bing platelets together)
Procoagulant activity
- phospholipid membrane of platelets used for 2 steps of coagulation cascade (10a and 2a)
What is your approach to bleeding disorders?
Non-hematologic - trauma, vessel abnormality Hematologic problem - platelet problem or VWF problem (primary) - coagulation factor problem (secondary)
What is your approach to a platelet problem?
Congenital
- Platelet receptor problem (bernard soulier syndrome, glanzmann thrombasthenia)
- Secretory problem (signal transduction)
- Granule storage problem (many….)
Acquired
- Drugs (aspirin, NSAIDs, clopidogrel, heparin)
- Systemic conditions (renal failure, cardiopulmonary bypass)
- Hematologic disease (myelodysplastic syndromes, myeloproliferative syndromes)
What is your approach to quantitative platelet problems?
Reduced production (nutritional, marrow infiltration, marrow failure, medications) increased destruction/consumption (ITP, sepsis, DIC MAHA, drug induced), increased sequestration (congestive, reactive, or infiltrative).
Describe heparin induced thrombocytopenia (HIT).
heparin-dependent antibody mediated platelet activation which leads to thromboembolic predisposition and consumptive thrombocytopenia. Basically binding cause platelet aggregation. Only 1-5% of heparin patients get this.
Describe DIC
Diffuse activation of coagulation cascade commonly caused by sepsis, malignancy or obstetrical catastrophe.
What is thrombotic thrombocytopenic purpura and what is the pentad of symptoms?
It’s a microvascular occlusive disorder. Classic pentad is thrombocytopenia, MAHA, fever, neurological symptoms, and renal impairment. 90% mortality if untreated. First two symptoms are most important.
How do you treat TTP?
Medical emergency!
Plasma exchange to remove autoantibody, aspirin, maybe corticosteroids.
What is unique about lymphoma?
Presents with enlarged lymph nodes. Lymphomas are solid malignancies, but cannot just be surgically resected. Can metastasize to the bone marrow as well. Two main types: Hodgkin and Non-Hodgkin.
What is the diagnostic indicator of Hodgkin lymphoma? And what is the main difference?
Reid Sternberg cell. Tumour consists of mostly reactive inflammatory cells, whereas non-hodgkin the cells are just malignant lymphocytes.
How do patients with acute myeloid and lymphoid leukaemia present?
With symptoms of cytopenias. Fatigue, SOB, bruises, B symptoms, etc.
What is multiple myeloma?
Proliferation of malignant plasma cells within the bone marrow. Causes pancytopenia and eats at the bone as well causing fractures.
Is myeloproliferative neoplasm basically another term for chronic myeloid leukaemia?
Yes. Just yes.
What are the main differences in clinical presentation between primary and secondary hemostasis?
Primary is skin and mucosal bleeding (mucocutaneous) whereas secondary is deep tissue bleeds (muscle, joints etc)
What is senile purpura?
An acquired vessel problem. Age dependent deterioration of the vascular supporting structure.
What is Von Willebrand Disease?
A congenital platelet problem. Bleeding disorder caused by inherited defects in concentration, structure, or function of VWF. Type 1 (most common) is not enough, type 2 is dysfunctional, type 3 there is none.
What is Hemophilia?
An inherited coagulation disorder with a deficiency of a coagulation factor. Hemo A is a factor 8 deficiency (more common) and Hemo B is a factor 9 deficiency. X-linked recessive inheritance.
