Hem & Onc - Pathology (Coagulation & platelet disorders, Hereditary hypercoagulability, & Blood transfusion therapy) Flashcards
Pg. 389-391 in First Aid 2014 or Pg. 359-360 in First Aid 2013 Sections include: -Coagulation disorders -Platelet disorders -Mixed platelet and coagulation disorders -Hereditary thrombosis syndromes leading to hypercoagulability -Blood transfusion therapy
Which coagulation pathways and factors does PT test?
Tests function of common and extrinsic pathway (i.e., factors I, II, V, VII, and X)
Which coagulation pathways and factors does PTT test?
Tests function of common and intrinsic pathway (all factors except VII and XIII)
In general, what kind of defect causes Hemophilia A or B? What are the specific defects?
Both intrinsic pathway coagulation defects; A: deficiency of factor VIII –> increased PTT; B: deficiency of factor IX –> increased PTT
What are the PT and PTT trends in Hemophilia A or B?
PT normal, PTT increased
What are the symptoms associated with Hemophilia A or B?
Macrohemorrhage in hemphilia - hemarthroses (bleeding into joints), easy bruising
What is the lab finding associated with Hemophilia A or B?
increased PTT
What is the treatment for hemophilia A?
Treatment: Recombinant factor VIII (in Hemophilia A)
What are PT and PTT trends in Vitamin K deficiency? What is the bleeding time associated with Vitamin K deficiency?
Both PT and PTT increase; Normal bleeding time
What kind of defect does Vitamin K deficiency cause?
General coagulation defect
Vitamin K deficiency decreases the synthesis of what substances?
Decrease synthesis of factors II, VII, IX, X, protein C, protein S
What causes an increased bleeding time?
Defects in platelet plug formation –> increased bleeding time (BT)
Name 3 effects of platelet abnormalities.
Platelet abnormalities –> (1) microhemorrhage: mucus membrane bleeding, epistaxis, petechiae, purpura, (2) increased bleeding time, (3) possible decreased platelet count (PC)
Give 4 examples of microhemorrhage that may occur as a result of platelet abnormalities.
microhemorrhage: mucus membrane bleeding, epistaxis, petechiae, purpura
What changes (if any) occur in platelet count (PC) and bleeding time (BT) with Bernard-Soulier syndrome?
PC decreased, BT increased
In general, what kind of defect is Bernard-Soulier syndrome? What is the specific defect, and what causes it?
Defect in platelet plug formation; Decreased GpIb –> defect in platelet-to-vWF adhesion
In general, what kind of defect is Glanzmann thrombasthenia? What is the specific defect, and what causes it?
Defect in platelet plug formation; Decreased GpIIb/IIIa –> defect in platelet-to-platelet aggregation
What lab finding is associated with Glanzmann thrombasthenia?
Labs: blood smear shows no platelet clumping
What changes (if any) occur in platelet count (PC) and bleeding time (BT) with Glanzmann thrombasthenia?
PC = no change, BT increased
What changes (if any) occur in platelet count (PC) and bleeding time (BT) with Immune thrombocytopenia?
PC decreased, BT increased
What is the specific defect in Immune thrombocytopenia, and what effect does it have?
Defect: anti-GpIIb/IIIa antibodies –> splenic macrophage consumption of platelet/antibody complex.
What may trigger Immune thrombocytopenia?
May be triggered viral illness.
How are platelets affected in Immune thrombocytopenia?
Decreased platelet survival
What lab finding is associated with Immune thrombocytopenia?
Labs: Increased megakaryocytes on bone marrow biopsy
What changes (if any) occur in platelet count (PC) and bleeding time (BT) with Thrombocytic thrombocytopenic purpura?
PC decreased, BT increased
What is the specific defect in Thrombocytic thrombocytopenic purpura, and what effect does it have?
Inhibition or deficiency of ADAMTS 13 (vWF metalloprotease) –> decreased degradation of vWF multimers
What is the pathogenesis of Thrombocytic thrombocytopenic purpura?
Pathogenesis: increased large vWF multimers –> increased platelet adhesion –> increased platelet aggregation and thrombosis
How are platelets affected in Thrombocytic thrombocytopenic purpura?
Decreased platelet survival
What are 2 lab findings associated with Thrombocytic thrombocytopenic purpura?
Labs: schistocytes, increased LDH
What are the symptoms associated with Thrombocytic thrombocytopenic purpura?
Symptoms: pentad of neurologic and renal symptoms, fever, thrombocytopenia, and microangiopathic hemolytic anemia
What is the treatment for Thrombocytic thrombocytopenic purpura?
Treatment: exchange transfusion and steroids
What are the changes to the following values in von Willebrand disease: (1) PC (2) BT (3) PT (4) PTT?
(1) No change (2) Increased (3) No change (4) No change or Increased
What are the changes to the following values in DIC: (1) PC (2) BT (3) PT (4) PTT?
(1) Decreased (2) Increased (3) Increased (4) Increased
What are the defects associated with von Willebrand disease, and what effects do they have?
(1) Intrinsic pathway coagulation defect: decreased vWF –> normal or increased PTT (depends on severity; vWF acts to carry/protect factor VIII). (2) Defect in platelet plug formation: decreased vWF –> defect in platelet-to-vWF adhesion.
How severe is von Willebrand disease, and how common is it?
Mild but most common inherited bleeding disorder.
What is the mode of inheritance of von Willebrand disease?
Autosomal dominant
How is von Willebrand disease diagnosed?
Diagnosed in most cases by ristocetin cofactor assay (decreased agglutination is diagnostic)
What is the treatment for von Willebrand disease, and how does it work?
Treatment: DDAVP, which releases vWF stored in endothelium
What is the pathogenesis of DIC?
Widespread activation of clotting leads to a deficiency in clotting factors, which creates a bleeding state.
What are 7 causes of DIC?
Causes: (1) Sepsis (gram-negative) (2) Trauma (3) Obstetric complications (4) acute Pancreatitis (5) Malignancy (6) Nephrotic syndrome (7) Transfusion; Think: “STOP Making New Thrombi”
What are 5 lab findings associated with DIC?
Labs: (1) schistocytes (2) increased fibrin split products (D-dimers) (3) decreased fibrinogen (4) decreased factors V and (5) VIII
What is the most common cause of inherited hypercoagulability in whites?
Factor V Leiden
What causes Factor V Leiden, and what is its effect?
Production of mutant factor V that is resistant to degradation by activated protein C
Where is the Prothrombin gene mutation, and what effects does it have?
Mutation in 3’ untranslated region –> increased production of prothrombin –> increased plasma levels and venous clots
What effects does inherited Antithrombin deficiency have versus not have?
Inherited deficiency of antithrombin: has no direct effect on the PT, PTT, or thrombin time but diminishes the increase in PTT following heparin administration.
What are 4 hereditary thrombosis syndromes leading to hypercoagulability?
(1) Factor V Leiden (2) Prothrombin gene mutation (3) Antithrombin deficiency (4) Protein C or S deficiency
What is the cause and effect of acquired Antithrombin deficiency?
Can also be acquired: renal failure/nephrotic syndrome –> antithrombin loss in urine –> increased factors II and X
What effect does Protein C or S deficiency have?
Decreased ability to activate factors V and VIII
For what outcome does Protein C or S deficiency increase the risk, and in what context?
Increased risk of thrombotic skin necrosis with hemorrhage following administration of warfarin
If a patient has skin and subcutaneous tissue necrosis after Warfarin administration, what condition should be on the differential diagnosis?
Skin and subcutaneous tissue necrosis after warfarin administration –> think protein C deficiency.; Think: “Protein C Cancels Coagulation”
What are 4 types of blood transfusion therapy?
(1) Packed RBCs (2) Platelets (3) Fresh frozen plasma (4) Cryoprecipitate
What is the dosage effect of blood transfusion therapy containing packed RBCs?
Increase Hb and O2 carrying capacity
What is the dosage effect of blood transfusion therapy containing platelets?
Increase platelet count (increase ~5000/mm^3/unit)
What is the dosage effect of blood transfusion therapy containing fresh frozen plasma?
Increase coagulation factor levels
What is the dosage effect of blood transfusion therapy containing cryoprecipitate?
Contains fibrinogen, factor VIII, factor XIII, vWF, and fibronectin
What are 2 clinical uses of blood transfusion therapy containing packed RBCs?
(1) Acute blood loss (2) Severe anemia
What is the general clinical use of blood transfusion therapy containing platelets? Give 2 specific examples of this use.
Stop significant bleeding (thrombocytopenia, qualitative platelet defects)
What are 4 clinical uses of blood transfusion therapy containing fresh frozen plasma?
(1) DIC (2) Cirrhosis (3) Warfarin overdose (4) Exchange transfusion in TTP/HUS
What is the clinical use of blood transfusion therapy containing cryoprecipitate?
Treat coagulation factor deficiencies involving fibrinogen and factor VIII
What are 5 risks of blood transfusions?
Blood transfusion risks include (1) infection transmission (low) (2) transfusion reactions (3) iron overload (4) hypocalcemia (citrate is a calcium chelator) (5) hyperkalemia (RBCs may lyse in old blood units).
Why is hypocalcemia a risk of blood transfusions?
Hypocalcemia (citrate is a calcium chelator)
Why is hyperkalemia a risk of blood transfusions?
Hyperkalemia (RBCs may lyse in old blood units)
