Platelets: Qualitative and Quantitative Disorders Flashcards
3 functions of von Willebrand Factor (vWF)
- Carrier protein for Factor VIII (VIII:C)
- Participates in platelet’s adhesion to subendothelial collagen
- Facilitates a normal aggregation response to ristocetin
von Willebrand disease
- Pathogenesis
Clinical disorder due to deficiency of vWF
von Willebrand disease
- Bleeding time results
Increased
von Willebrand disease
- Closure time results (PFA)
Increased
von Willebrand disease
- Platelet adhesion result
Abnormal
von Willebrand disease
- Platelet aggregation w/ ristocetin
Abnormal ristocetin induced aggregation
von Willebrand disease
- Platelet count
Can be normal or abnormal → not a hallmark
von Willebrand disease
- APTT result
Prolonged due to ↓ VIII:C
Bernard-Soulier syndrome
- Pathogenesis
Missing GPIb/IX receptor complex
- Platelets cannot adhere to subendothelium via vWF
Bernard-Soulier syndrome
- Bleeding time result
Prolonged
Bernard-Soulier syndrome
- Platelet aggregation w/ ADP and ristocetin
- ADP: normal
- Ristocetin: abnormal
Bernard-Soulier syndrome
- Platelet adhesion result
Abnormal
Bernard-Soulier syndrome
- Platelet count
Decreased
Bernard-Soulier syndrome
- Platelet morphology
Giant platelets
Glanzmann’s thrombasthenia
- Pathogenesis
Missing GPIIb/IIIa receptor complex
- Platelets cannot bind to fibrinogen and bridge/attach to one another → cannot aggregate
Glanzmann’s thrombasthenia
- Bleeding time result
Prolonged
Glanzmann’s thrombasthenia
- Platelet adhesion result
Normal
Glanzmann’s thrombasthenia
- Platelet aggregation w/ ADP and ristocetin
- ADP: abnormal
- Ristocetin: normal
Glanzmann’s thrombasthenia
- Platelet count
Normal
Glanzmann’s thrombasthenia
- Platelet morphology
Normal
5 acquired qualitative platelet disorders
- Drug therapy (most common cause)
- Renal disease (uremia)
- Dysproteinemias
- Liver disease
- Platelet Abs
4 general causes for thrombocytopenia
- ↓ platelet production
- Ineffective thrombopoiesis
- Abnormal distribution of platelets
- ↑ destruction of platelets
Destruction occurs by processes other than the immune system (consumption, mechanical destruction)
Nonimmune-mediated platelet destruction
Platelets become sensitized w/ Abs and RES, especially the spleen, destroys them
Immune-mediated platelet destruction
3 causes of nonimmune-mediated platelet destruction for thrombocytopenia
- Thrombotic thrombocytopenic purpura (TTP)
- Hemolytic uremic syndrome (HUS)
- Disseminated intravascular coagulation (DIC)
3 causes of immune-mediated platelet destruction for thrombocytopenia
- Idiopathic thrombocytopenic purpura (ITP)
- Drug-induced → heparin-induced thrombocytopenia (HIT)
- Neonatal alloimmune thrombocytopenia
Thrombocytopenic purpura (TTP) - Predisposing factors
- Infectious diseases
- Autoimmune diseases
- Drugs
- Pregnancy
- Hereditary
Thrombocytopenic purpura (TTP) - Clinical presentation
Characterized by
- MAHA (jaundice, pallor, acute renal failure)
- Thrombocytopenia
- Neurologic dysfunction (headaches, seizures, vertigo, delirium)
Mostly in adults
Thrombocytopenic purpura (TTP) - Platelet count
Decreased
Thrombocytopenic purpura (TTP) - Lab findings
- ↓ RBC, hemoglobin, hematocrit
- ↑ reticulocytes
- SCHISTOCYTES
- Coag tests (PT, APTT) usually normal but it helps to distinguish from DIC
Thrombocytopenic purpura (TTP) - Type of anemia/mechanism
Hemolytic anemia???
Underlying disorder that damages vascular endothelium*
- Caused by ultra high molecular weight vWF multimers present when endothelium-secreted vWF isn’t properly proteolysed by its cleaving protease
- Promotes deposition of platelet thrombi (platelet consumption, fragmented RBCs leading to intravascular hemolysis)
Hemolytic uremic syndrome (HUS)
- Predisposing factors
Acquired disorder that resembles TTP
Characterized by
- MAHA
- Thrombocytopenia
Hemolytic uremic syndrome (HUS)
- Clinical presentation in contrast to TTP
- Usually no neurological manifestations
- Intravascular clotting confined to the kidney leading to acute renal failure
- Associated w/ bacterial toxins
Hemolytic uremic syndrome (HUS)
- Platelet count
Decreased
Hemolytic uremic syndrome (HUS)
- Lab findings
- Similar to TTP
- Additionally, abnormal urinalysis results: proteinuria, hematuria, RBC casts often
Hemolytic uremic syndrome (HUS)
- Clinical findings in children
- Classic HUS occurs in infants <2 yrs age
- Children present after a febrile illness with: vomiting, bloody diarrhea, MAHA leads to renal failure, hypertension
Hemolytic uremic syndrome (HUS)
- Clinical findings in adults
Link w/ malignancy and/or chemotherapy
Acute idiopathic (immune) thrombocytopenic purpura (ITP) - Age of onset
Childhood
Acute idiopathic (immune) thrombocytopenic purpura (ITP) - Previous infections?
Common
Acute idiopathic (immune) thrombocytopenic purpura (ITP) - Platelet count
Decreased (< 20,000/uL), so BM exam requested
Acute idiopathic (immune) thrombocytopenic purpura (ITP) - Bleeding characteristics
Abrupt onset of bruising, petechiae, and sometimes mucosal bleeding in a previously healthy patient
Acute idiopathic (immune) thrombocytopenic purpura (ITP) - Occurrence of spontaneous remission
Occurs in majority of patients
Acute idiopathic (immune) thrombocytopenic purpura (ITP) - Treatment
- Some patients do not require treatment due to spontaneous remissions
- Severe causes require platelet transfusions and/or splenectomy (as spleen is primary site of platelet destruction)
Chronic idiopathic (immune) thrombocytopenic purpura (ITP) - Age of onset
20-50 years old, females over males
Chronic idiopathic (immune) thrombocytopenic purpura (ITP) - Previous infections?
Usually not associated
Chronic idiopathic (immune) thrombocytopenic purpura (ITP) - Platelet count
Variable, 30,000-80,000/uL
Chronic idiopathic (immune) thrombocytopenic purpura (ITP) - Bleeding characteristics
Insidious
Chronic idiopathic (immune) thrombocytopenic purpura (ITP) - Occurrence of spontaneous remission
Relatively rare
Chronic idiopathic (immune) thrombocytopenic purpura (ITP) - Treatment
- Treat w/ steroids
- Refractory cases may require splenectomy and/or chemotherapeutic agents
Heparin-induced thrombocytopenia (HIT), type II, according to the basis for the possible thrombotic and hemorrhagic presentation
- In HIT, PF4 and heparin combine to form a surface complex against which the IgG antibody is directed
- Platelets become activated, in vivo platelet aggregation with thrombosis is possible → thrombotic and hemorrhagic problems
An adverse effect of heparin therapy is called ____
Heparin-induced thrombocytopenia (HIT)
Develops when the mother lacks a specific platelet-specific Ag that the fetus has inherited from the father
Neonatal alloimmune thrombocytopenia
How do we get thrombocytopenia in neonatal?
Mother produces Abs to the fetal Ag which cross the placenta, and attach to the Ag-bearing fetal platelets, resulting in thrombocytopenia
This is autosomal dominant inheritance and giant dohle-like bodies in neutrophils, eosinophils, basophils, and monocytes are seen
May-Hegglin anomaly
4 clinical states in which thrombocytosis can be seen
- Hemorrhage or surgery
- Inflammation
- Exercise-induced
- FDA
Describe thrombocytosis according to the etiology and the platelet count values
- Etiology: reactive phenomena–secondary to hemorrhage or surgery, inflammation, exercise-induced, FDA???
- Platelet count is ↑ but usually <1,000,000/cumm
Describe thrombocythemia according to the etiology and the platelet count values
- Etiology: MP disorder cause is unknown
- Platelet count exceeds 1,000,000/cumm