Notes
Hemostatic Disorders (Platelet & Coagulation Disorders)
Sections
Overview
Hemostasis is the process of platelet plug formation and coagulation to stop bleeding.
Disorders occur as the results of imbalance in hemostatic forces.
– Excessive bleeding is the result of vessel wall defects, platelet disorders, and coagulation disorders.
– Excessive clotting occurs in hypercoagulation states, and leads to thrombosis of the arteries and veins.
Platelet Disorders
von Willebrand disease
Characterized by deficient levels of von Willebrand factor, which is responsible for platelet adhesion and acts as a binding protein for coagulation factor VIII.
Recall that von Willebrand factor is crucial in the early stages of hemostasis, in which it acts as a bridge between circulating platelets and exposed subendothelial collagen; after their activation, von Willebrand factor bridges adjacent platelets.
von Willebrand disease is inherited as a genetic mutation, with three types:
Type 1 is the most common, and least severe; it is characterized by decreases in von Willebrand factor and coagulation factor VIII levels.
Type 2 is intermediate, and comprises several subtypes that vary in severity.
Type 3 is rare, but severe, and is characterized by nearly absent von Willebrand factor and factor VIII.
Be aware that von Willebrand disease can also be acquired, though this is rare.
Treatment includes desmopressin (ex: DDAVP), which induces release of von Willebrand factor and Factor VIII from the endothelium, and/or von Willebrand factor replacement therapy.
Thrombocytopenia
Characterized by platelet counts below 150 thousand per microliter of blood; normal platelet count is between 150-450 thousand per microliter of blood.
The causes of thrombocytopenia include:
Decreased platelet production in the bone marrow
Increased sequestration (particularly in the spleen)
Increased platelet destruction
Severity and treatment for thrombocytopenia depends on its causes.
A notable characteristic of mild to severe thrombocytopenia is the appearance of petechiae, which are small reddish purple spots caused by blood leakage from capillaries. Recall that thousands of small nicks occur in the walls of the blood vessels each day; without sufficient platelet populations and plug formation, bleeding ensues.
Coagulation Disorders
Coagulation disorders occur when coagulation factors are insufficient or absent and clot formation is impaired.
Hemophilia
Hemophilia is a congenital disorder that, because it is x-linked, primarily affects males.
There are two main types of hemophilia: A and B.
Hemophilia A is characterized by absent or deficient factor VIII; this is the most common form and results from a mutation of the F8 gene.
Hemophilia B is characterized by absent or deficient factor IX; it results from a mutation of the F9 gene.
To understand their pathogenesis, quickly review a portion of the coagulation cascade:
Activated factor IX, complexed with activated co-factor VIII and calcium ions, activates factor X. In turn, activated factor X complexes with activated cofactor V and calcium ions to form prothrombinase. Prothrombinase then converts prothrombin to thrombin, which converts fibrinogen to fibrin, which creates a mesh-like clot surrounding blood cells and other circulating molecules.
Treatment for hemophilia typically involves replacement of the deficient factor.
Common bleeding sites in hemophilia include the oral mucosa and musculoskeletal sites; hemophilia is characterized by hemarthrosis, which is bleeding into the joint spaces. Intracerebral and gastrointestinal bleeding can be fatal.
Vitamin K Deficiency
Vitamin K is necessary for hepatic synthesis of prothrombin, factors VII, IX, and X.
Two key sources of vitamin K are the diet (especially green, leafy vegetables) and bacterial production (in the proximal intestine).
From the GI tract, vitamin K is absorbed and transported to the liver, where it is used to synthesize four of the coagulation factors.
These factors are then carried in the blood, ready to participate in the coagulation cascade and production of thrombin.
Thus, if the quantity of vitamin K present in GI tract is insufficient, or it is not properly absorbed and transported to the liver, thrombin production and clot formation will be impaired.
Be aware that liver diseases can also inhibit the production of coagulation factors, independent of vitamin K deficiencies.
Thrombosis
Excessive clot formation obstructs blood flow, which can lead to ischemia and organ failure.
Treatment: When clots have formed and acute treatment is necessary, fibrinolytic (aka, thrombolytic) drugs, such as streptokinase, tissue-type plasmin activator, or urokinase are administered. Thus, fibrinolytic drugs can be life-saving when clots obstruct blood flow in the lungs, myocardium, or the brain.
Risk factors for arterial and venous thrombosis are similar, and include age, surgery, trauma, cancer, and pregnancy (the risk of thromboembolism increases 4-5 fold in pregnant women, and accounts for approximately 15% of maternal death during pregnancy).
Arterial and venous thrombosis are similar in many ways, but can have different mechanisms of pathogenesis.
Arterial thrombosis tends to result from excessive platelet aggregation.
Because arterial thrombosis blocks delivery of oxygenated blood to the organs, including the heart and brain, it can be deadly.
Prevention of arterial thrombosis typically relies upon antiplatelet treatments, such as aspirin or ADP receptor inhibitors that prevent platelet aggregation.
Deep vein thrombosis tends to result from clot formation in the valvular cusps.
Pulmonary embolism, which can block blood flow to the lungs, is a major clinical concern in patients with deep vein thrombosis.
Prevention typically relies on anticoagulants, such as exogenous heparin and warfarin, etc.
Board Review
Von Willebrand's Disease
Getting ready for boards? Review these concise, bulleted high yield reviews for your exam.
USMLE & COMLEX-USA
Nurse Practitioner (NP)
Physician Assistant (PA)
Internal Medicine (ABIM)
Hemophilia
Getting ready for boards? Review these concise, bulleted high yield reviews for your exam.
USMLE & COMLEX-USA
Nurse Practitioner (NP)
Physician Assistant (PA)
Internal Medicine (ABIM)
References
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