Lecture 12 Flashcards
Hemostasis
Arrest of bleeding (blood clotting) caused by activation of the blood coagulation mechanism
Causes of Hemostasis
Trauma, inflammatory or neoplastic damage, vessel erosion, congenital malformations
Balance of Hemostasis
Maintain blood fluidity/stop flow rapidly when the system is compromised to prevent blood loss
Factors concerned with proper function of hemostasis
Integrity of small blood vessels (and lining: endothelium), Adequate numbers of platelets, Normal amounts of coagulation factors (proteins and factors (Ca ions) in blood), Normal amounts of coagulation inhibitors
Importance of small blood vessels
First line of defence, constrict on injury using a clot, prevents coagulation, exposure of underlying connective tissue of the endothelium allows for platelet adhesion, activates coagulation mechanism (release of vasoconstriction and coagulation factors)
Factors that can compromise hemostasis
Abnormality of small blood vessels, Injury or disease of the bone marrow which damages megakaryocytes, liver/kidney damage, overconsumption of coagulation factors
Thrombocytopenia
Low levels of platelets are observed or abnormal platelet function
Platelets
Small fragments of cytoplasm from large precursor cells called megakaryocytes which have a lifespan of about 10 days
Platelet function
Plug defects in the vessel wall, Liberate vasoconstrictors from granules (serotonin, ADP, thromboxane A2) and compounds causing platelets to aggregate (ADP, thromboxane A2), Contain granules that release factors that initiate and promote coagulation upon activation
Primary Hemostasis
Platelet plug
Secondary Hemostasis
Coagulation factors culminate in the production of fibrin mesh to stabilize the platelet plug.
Abnormal platelet function can cause…
Leukemia (bone marrow injury, will need cancer treatment), autoimmune destruction, and petechiae hemorrhage
Petechiae
A hemorrhage indicative of thrombocytopenia or defective platelet function that is less than 2mm in diameter which does not blanch when pressed
Causes of Coagulation Disturbances
Deficiency of one or more plasma coagulation factors, Insufficient supply of calcium ions, Liberation of thromboplastic material into circulation, Vitamin K deficiency, Drugs like NSAIDS, Heparin, Genetic diseases (Von Willebrand and Hemophilia), and liver/kidney disease
NSAIDS
A drug; Causes coagulation disturbances by blocking thromboxane synthesis
Heparin
A drug; causes coagulation disturbances through a decrease in platelets (Inhibits synthesis of active vitamin K)
Blood Coagulation Factors
Highly complex chain reaction, 3 phases to develop a blood clot
How does Plasminogen-plasmin dissolve clots?
By breaking down fibrin into degradation products (FDP) – can be used to measure deep vein thrombosis, embolism, DIC
Coagulation Inhibitors
Antithrombin III (inhibits factor 2a in cascade)
and Protein C and S (Inactivates factors V and VIII); Circulate in blood plasma, produced by the liver
Hemophilia A
Disturbances of Blood Coagulation; are more common(factor VIII deficiency)
Hemophilia B
Disturbances of Blood Coagulation; less common (factor IX deficiency)
von Willebrand disease
Disturbances of Blood Coagulation; low levels of specific clotting proteins in the blood (von Willebrand factor forms the framework for platelets and coagulation factors to form a clot)
Hemophilia
X-linked hereditary disease, Episodes of hemorrhage in joints and internal organs after a minor injury
Severe liver disease
Impairs synthesis of adequate amounts of coagulation factors (Vitamin K, Ca2+)
When does Inadequate synthesis of Vitamin K occur?
Occurs if the intestinal bacteria have been eradicated with prolonged use of antibiotics
When does Inadequate absorption of Vitamin K occur?
Occurs in blockage of the common bile duct by a gallstone or tumour, preventing bile from entering the intestine to promote absorption of vitamin
Factors that result in intravascular coagulation
Diseases associated with systemic shock and tissue necrosis, Overwhelming bacterial infections, tissue necrosis (cancer, trauma), and pregnancy (amniotic fluid embolism, placental abruption)
Disseminated intravascular coagulation (DIC)
In conditions where clotting and fibrinolysis are occurring, consumption of factors results in widespread failure of hemostasis - Results in widespread bleeding, clotting- Multi-organ failure (anticoagulation treatment required)
Thrombotic Thrombocytopenic purpura (TTP)
Deficiency of VWF cleaving protein ADAMTS1 which results in platelet aggregation and damage leading to clotting and multi-organ thrombosis, fragmentation of RBC (schistocytes) causing anemia and thrombocytopenia
Treatment for TTP
Plasma exchange (remove VWF fragments), immune suppressive therapy/ corticosteroids, Splenectomy to remove cells creating antibodies against ADAMTS1
ITP (Immune thrombocytopenic Purpura)
Development of autoimmune antibodies against platelets which target the destruction of platelets by splenic macrophages (Children recover but in adults this is chronic)
ITP therapies
Corticosteroids/immune suppressive agents, IVIG (non-specific binding to macrophage receptors),
IV Anti-D IG (targets RBC as well), splenectomy
Infectious causes of clotting disorders
Systemic Infections (DIC, TTP, and Vasculitis), Bacterial, Gram-ve sepsis (meningococcemia), non-specific (CMV, HIV, HCV), Parainfluenza, Mumps, Adenovirus), Specific (Hemorrhagic viruses)
Ebola (+symptoms)
Spread by direct contact with bodily fluids (2-20 inc phase) and causes infection + destruction of monocytes/macrophages/DC and spreads to LN; symptoms include (sore throat, fever, muscle pain), 25-90% fatal vaccine available and some antivirals
Marburg
Similar to Ebola but has a much worse prognosis (90% fatality and survivors have severe long-term effects due to organ damage)
Laboratory Tests to Evaluate Hemostasis
Platelet count (CBC), Fibrinogen levels in the blood, kidney/liver function, Bleeding and clotting time, etc.
Schistocytes
damaged blood cells (DIC / TTP)
D-dimers
fibrinolytic activity (Fibrin Degradation Product)
Partial thromboplastin time (PTT)
The time it takes for blood plasma to clot after a lipid substance and calcium are added to the plasma sample; measures time of first phase coagulation (extrinsic)
Prothrombin time (PT)
Measures time it takes for blood to clot after adding thromboplastin; prolonged time indicates an abnormality in second or third phases of coagulation; used to measure effects of warfarin (intrinsic, common)
Thrombin time (TT)
Bypasses the first two phases of blood coagulation, primarily measures the level of fibrinogen
Treatments
Treat the underlying cause, add blood products (RBC, fresh frozen plasma, cryoprecipitate (enriched in fibrinogen), Platelet transfusion