Abnormal Hemostasis Flashcards
What is APTT?
Activated partial thromboplastin time (APTT) is a medical test that characterizes blood coagulation. It is an indicator of the Intrinsic Pathway.
What is PT/INR?
Prothrombin time (PT) and international normalized ratio (INR) are assays that evaluate the Extrinsic Pathway.
Thrombocytosis
Increased platelet count
Thrombocytopenia
Decreased platelet count
Primary fibrinolysis
In primary fibrinolysis, fibrinogen is converted into fibrinogen degradation products.
Secondary fibrinolysis
In secondary fibrinolysis both fibrin and fibrinogen are digested by plasmin.
What are the categories of quantitative platelet disorders?
Thrombocytopenia
Thrombocytosis
What are some of the common causes of thrombocytopenia?
- Bone marrow hypoplasia
- Hereditary thrombocytopenia
- Drug induced thrombocytopenia
Immune thrombocytopenic purpura (ITP)
Presentation with purpura on the skin and increased bleeding due to IgG mediated autoimmunity resulting in low platelets
Thrombotic thrombocytopenic purpura (TTP)
Cause formation of microscopic thrombi that can damage organs due to the inhibition of ADAMTS13 which results in multimers of vWF to increase in the blood and increase the amount of platelets in adhesion.
How does aspirin alter platelets?
It blocks the formation of thromboxane A2 as it is a COX inhibitor which leads to the inhibition of platelet aggregation
Glanzmann’s Thrombasthenia
Defect in GP IIb and IIIa that interferes with platelet aggregation and increases the bleeding time
Bernard-Soulier Disease
Defect in GP Ib prevents platelet adhesion which will increase the bleeding time
Storage Pool Disease
Decrease in the number of dense granules so aggregation is interfered with and bleeding is prolonged.
What are some causes of thrombocytosis?
- Splenectomy
- Reaction to cancer/drugs/infection
- Autonomous increase in platelets (thrombocythemia)
What are qualitative platelet disorders?
Platelet numbers are usually normal, however, platelet function is impaired.
What are some causes of qualitative platelet disorders?
- Disease induced platelet defects
- Drug induced platelet defects
- Diet induced platelet defects
What is the cause and manifestation of Gray Platelet Syndrome?
Lack of alpha granules. Present with purpura of unknown origin.
How does Omega-3 affect platelet function?
Blocks generation of thromboxane A2
Polycythemia Vera
Cancer of the red cell and there is a high production in the amount of RBCs
What are the 3 categories of vascular disorders that lead to bleeding?
- Subendothelial
- Endothelial
- Mechanical
What is an example of a congenital sub endothelial disorder?
Ehler Danlos Syndrome
What are some symptoms of Ehler Danlos Syndrome?
Hypermobile joints. Hyperflexible skin, osteogenesis imperfecta, drugs, infections, amyloidosis.
Telangiectasias
Small dilated blood vessels near surface of skin
What are examples of congenital endothelial disorders?
Telangiectasia (HHT)
Arteriovenous malformation
Giant hemangioma (Kasaback- Merritt syndrome)
What is a nutritional disorder that can affect bleeding?
Scurvy
What are examples of bleeding disorders due to coagulation factor abnormalities?
Hemophilias
von Willebrand’s Disease
Hemophilia A
VIII coagulation factor deficiency
Hemophilia B
IX coagulation factor deficiency
What pathway does Hemophilia A and B affect?
Intrinsic
What is the effect of hemophilia on APTT?
It is elevated
What is the effect of hemophilia on platelet function?
Normal Platelet Function
What is the effect of hemophilia on bleeding time?
Normal bleeding time
von Willebrand’s Disease with Types 1, 2 and 3
- Type-1 and Type-3 von Willebrand’s diseases are characterized by a decrease in the circulating level of the factor.
- Type-2 von Willebrand’s disease is characterized by a qualitative defect in the protein.
What is the effect of vW’s disease on APTT?
Slightly elevated
What is the effect of vW’s disease on platelet function?
Impaired platelet adhesion
What is the effect of vW’s disease on bleeding time?
Increased bleeding time
What can excessive activation of the fibrinolytic system cause?
Bleeding
What is the D-dimer test used for?
It tests for fibrin degradation products and is used to assess DIC/DVT states.
What can lead to Disseminated Intravascular Coagulation (DIC)?
Sepsis
Tissue Destruction
Endothelial Injury
What is DIC?
Disseminated Intravascular Coagulation. Occurs when both fibrinogen and fibrin are degraded by plasmin which consumes clotting factors and platelets leading to bleeding.
What can α2-antiplasmin deficiency cause?
Increased fibrinolysis and bleeding
Heparin Induced Thrombocytopenia
Platelet Factor 4 complexes with heparin and causes and antibody response which leads to HIT as platelets are targeted by antibodies
What is bleeding in HIV mainly associated with?
Thrombocytopenia
Which of the blood clotting tests is commonly used for the diagnosis of Hemophilias?
A. Activated partial thromboplastin time
B. Prothrombintime/INR
C. Thrombin time
D. Bleeding time
E. Fibrinogenlevels
A. Activated partial thromboplastin time
A patient was admitted to the hospital with an urinary tract infection. Two days later he developed fever and his coagulation parameters and platelet count became abnormal. Additional test showed D-dimer positive and positive blood cultures for E. Coli. What is the likely diagnosis of this patient? A. DIC B. Hemophilia B C. Hypercoagulable state D. APC Resistance E. Von Willebrand disease
A. DIC
Factor V Leiden
Abnormal V is cleaved to Va and it is resistant to Protein C cleavage which leads to thrombophilia leading to increased clotting
Prothrombin 20210A
Elevated plasma prothrombin levels leads to an increase in venous thrombosis.
Hyperhomocysteinemia
Methylene tetrahydrofolate reductase mutation (mtHfr C677t) results in a moderate increase in serum homocysteine, which is associated
with both arterial and venous thrombosis.
