Lecture 12

Question 1

Hemostasis

Answer 1

Arrest of bleeding (blood clotting) caused by activation of the blood coagulation mechanism

Question 2

Causes of Hemostasis

Answer 2

Trauma, inflammatory or neoplastic damage, vessel erosion, congenital malformations

Question 3

Balance of Hemostasis

Answer 3

Maintain blood fluidity/stop flow rapidly when the system is compromised to prevent blood loss

Question 4

Factors concerned with proper function of hemostasis

Answer 4

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

Question 5

Importance of small blood vessels

Answer 5

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)

Question 6

Factors that can compromise hemostasis

Answer 6

Abnormality of small blood vessels, Injury or disease of the bone marrow which damages megakaryocytes, liver/kidney damage, overconsumption of coagulation factors

Question 7

Thrombocytopenia

Answer 7

Low levels of platelets are observed or abnormal platelet function

Question 8

Platelets

Answer 8

Small fragments of cytoplasm from large precursor cells called megakaryocytes which have a lifespan of about 10 days

Question 9

Platelet function

Answer 9

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

Question 10

Primary Hemostasis

Answer 10

Platelet plug

Question 11

Secondary Hemostasis

Answer 11

Coagulation factors culminate in the production of fibrin mesh to stabilize the platelet plug.

Question 12

Abnormal platelet function can cause…

Answer 12

Leukemia (bone marrow injury, will need cancer treatment), autoimmune destruction, and petechiae hemorrhage

Question 13

Petechiae

Answer 13

A hemorrhage indicative of thrombocytopenia or defective platelet function that is less than 2mm in diameter which does not blanch when pressed

Question 14

Causes of Coagulation Disturbances

Answer 14

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

Question 15

NSAIDS

Answer 15

A drug; Causes coagulation disturbances by blocking thromboxane synthesis

Question 16

Heparin

Answer 16

A drug; causes coagulation disturbances through a decrease in platelets (Inhibits synthesis of active vitamin K)

Question 17

Blood Coagulation Factors

Answer 17

Highly complex chain reaction, 3 phases to develop a blood clot

Question 18

How does Plasminogen-plasmin dissolve clots?

Answer 18

By breaking down fibrin into degradation products (FDP) – can be used to measure deep vein thrombosis, embolism, DIC

Question 19

Coagulation Inhibitors

Answer 19

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

Question 20

Hemophilia A

Answer 20

Disturbances of Blood Coagulation; are more common(factor VIII deficiency)

Question 21

Hemophilia B

Answer 21

Disturbances of Blood Coagulation; less common (factor IX deficiency)

Question 22

von Willebrand disease

Answer 22

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)

Question 23

Hemophilia

Answer 23

X-linked hereditary disease, Episodes of hemorrhage in joints and internal organs after a minor injury

Question 24

Severe liver disease

Answer 24

Impairs synthesis of adequate amounts of coagulation factors (Vitamin K, Ca2+)

Question 25

When does Inadequate synthesis of Vitamin K occur?

Answer 25

Occurs if the intestinal bacteria have been eradicated with prolonged use of antibiotics

Question 26

When does Inadequate absorption of Vitamin K occur?

Answer 26

Occurs in blockage of the common bile duct by a gallstone or tumour, preventing bile from entering the intestine to promote absorption of vitamin

Question 27

Factors that result in intravascular coagulation

Answer 27

Diseases associated with systemic shock and tissue necrosis, Overwhelming bacterial infections, tissue necrosis (cancer, trauma), and pregnancy (amniotic fluid embolism, placental abruption)

Question 28

Disseminated intravascular coagulation (DIC)

Answer 28

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)

Question 29

Thrombotic Thrombocytopenic purpura (TTP)

Answer 29

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

Question 30

Treatment for TTP

Answer 30

Plasma exchange (remove VWF fragments), immune suppressive therapy/ corticosteroids, Splenectomy to remove cells creating antibodies against ADAMTS1

Question 31

ITP (Immune thrombocytopenic Purpura)

Answer 31

Development of autoimmune antibodies against platelets which target the destruction of platelets by splenic macrophages (Children recover but in adults this is chronic)

Question 32

ITP therapies

Answer 32

Corticosteroids/immune suppressive agents, IVIG (non-specific binding to macrophage receptors),
IV Anti-D IG (targets RBC as well), splenectomy

Question 33

Infectious causes of clotting disorders

Answer 33

Systemic Infections (DIC, TTP, and Vasculitis), Bacterial, Gram-ve sepsis (meningococcemia), non-specific (CMV, HIV, HCV), Parainfluenza, Mumps, Adenovirus), Specific (Hemorrhagic viruses)

Question 34

Ebola (+symptoms)

Answer 34

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

Question 35

Marburg

Answer 35

Similar to Ebola but has a much worse prognosis (90% fatality and survivors have severe long-term effects due to organ damage)

Question 36

Laboratory Tests to Evaluate Hemostasis

Answer 36

Platelet count (CBC), Fibrinogen levels in the blood, kidney/liver function, Bleeding and clotting time, etc.

Question 37

Schistocytes

Answer 37

damaged blood cells (DIC / TTP)

Question 38

D-dimers

Answer 38

fibrinolytic activity (Fibrin Degradation Product)

Question 39

Partial thromboplastin time (PTT)

Answer 39

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)

Question 40

Prothrombin time (PT)

Answer 40

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)

Question 41

Thrombin time (TT)

Answer 41

Bypasses the first two phases of blood coagulation, primarily measures the level of fibrinogen

Question 42

Treatments

Answer 42

Treat the underlying cause, add blood products (RBC, fresh frozen plasma, cryoprecipitate (enriched in fibrinogen), Platelet transfusion