Hemostasis Flashcards
1
Q
4 Stages of Normal Hemostasis
A
- 1- endothelial injury —> transient vasoconstriction to dec blood flow to site
- 2- primary homeostasis- exposed sub endothelial matrix —> platelet adhesion, activation and aggregation
- 3- secondary homeostasis - tissue factor —> coagulation cascade —> forming fibrin clot
- 4- fibrinolysis - counter-regaultion to dissolve clot/ restrict it to only site of injury
2
Q
2 Types of Thrombi
A
- White: mainly platelets forming platelet plaque; arteries
- Red: mainly RBCs forming thrombin; veins
3
Q
How are endothelial cells pro-thrombiotic?
A
- Sub endothelial cells express von Willebrand factor once exposed (glue b/n thrombogenic vessel wall and Gp1b receptors of platelets) platelet adhesion
- Activated endothelial cells make tissue factor —> extrinsic cascade AND secrete plasminogen activator inhibitor —> promotes thrombosis/dec fibrinolysis
4
Q
How are endothelial cells anti-thrombiotic?
A
- Endothelial prostacyclin (PG12) and NO —> vasodilation, muscle relax, inhibit platelet aggregation
- Adenosine disphosphatase degrades ADP (ADP normally inc aggregation)
- Heparin-like molecules which interact w/ antithrombin III to enhance it
- Thrombomodulin - activates protein C which cleaves factors 5a and 8a
- Tissue Factor Pathway Inhibitor - (TFPI) inactivates factor Xa and tissues factor 7a complex
- tPA- activates plasminogen —> plasmin (major fibrinolytic agent)
5
Q
2 Types of Platelet Granules
A
- Alpha granules - fibrinogen, vWF, clotting factors V and VIII, platelet factor 4, PDGF and p-selectin
- Delta granules - ADP, ATP, Ca++, serotonin, epi
6
Q
Primary Hemostasis
A
- Adhesion —> shape change —> platelets secrete granules (platelet activation) —> activated platelets now secrete TxA2 (vasoconstrictor that stimulates platelet aggregation) and delta granules secrete ADP (mediator of aggregation)
- Platelets (aggregates) held together by fibrinogen and GpIIb/IIIa receptors on platelets (cross links); GpIIb/IIIa inhibitors used as anticoagulants
Concomitant activation of thrombin stabilizes the platelet plug
7
Q
Closure Time
A
- Meas time required for platelet sample to plug a tube
- ID low platelet function if prolonged but does not tell cause
- Could be low platelet count, anti-platelet meds, reduction of proteins needed for platelet function, etc
- Can screen for Von Willebrand Disease but not all platelet function disorders AND cannot predict risk of preoperative bleeding
8
Q
Secondary Hemostasis
A
**Coag Cascade
- Series of amplifying enzymatic reactions that ends in thrombin (2A) activation —> fibrin (1a) formation
- Each factor starts as a proenzyme (inactive form) then activated and can go on to act as enzyme in subsequent reactions
- Each reaction requires activated enzyme, cofactor, proenzyme and phospholipid surface as scaffold
- Also use Ca++ ions (from delta granules)
9
Q
Extrinsic Path of Coag Cascade
A
Tissue injury —> tissue factor + 7a —> activates 10 —> activates prothrombin to thrombin (2) —> converts fibrinogen to fibrin (1a) AND activates factor 8 which helps in intrinsic path AND activates factor 13 which stabilizes fibrin polymers
10
Q
PT
A
- Screens extrinsic path; add tissue factor and phospholipids to plasma; prolonged PT and normal aPTT suggest factor VII deficiency (affected by warfarin)
- INR- international std ratio to compare PT b/n labs
11
Q
Intrinsic Path of Coag Cascade
A
Factor 12 (Hageman Factor) is activated by HMWK collagen —> activates 11 —> activates 9 —> w/ help from factor 8 they activated factor 10 —> activates prothrombin to thrombin (2) —> converts fibrinogen to fibrin (1a) AND activates factor 13 which stabilizes fibrin polymers
12
Q
aPTT
A
Screens intrinsic path (12, 11, 9, 8); prolonged if deficiency in one of these factors; Von Will Disease; lupus anticoagulant disorder; heparin use
13
Q
4 Roles of Thrombin
A
- Converts fibrinogen to fibrin
- Activates factors 11, 5 and 8
- Platelet activation through PARs
- Pro-inflammatory
14
Q
2 Inhibitors of Coagulation Prod by Liver
A
- Antithrombin III - inactivates thrombin (2) and inhibits 9a-12a (heparin potentiates antithrombin III)
- Activated protein C - inhibits factors 5a and 8a; requires protein S co-factor and both require Vit K (so inhibited by warfarin)
15
Q
Fibrinolysis
A
- Fibrinolytic cascase is mainly carried out by plasmin (breaks down fibrin —> D-dimers)
- Plasminogen —> plasmin activated by tPA, urokinase-like plasminogen activator and streptokinase (bacterial product)
16
Q
von Willebrand Disease
A
deficiency in VWF - bleeding disorder
17
Q
Bernard Soulier Disease
A
- deficiency in Gpb1 receptor; defective platelet adhesion to endo wall
18
Q
Glanzmann Thrombasthenia
A
- deficiency in GpIIb/IIIa receptor; bleeding disorder b/c cannot aggregate
19
Q
4 Types of Hemorrhage
A
Hematoma- more of a solid lump; accumulation of blood enclosed in tissue or brain
- Petechiae - tiny (1-2 mm); usually due to platelet dysfunction/deficiency or loss of vascular wall support
- Purpura - medium (3-5 mm); similar causes to petechiae but also vasculitis (infection compromises vessel wall)
- Ecchymoses- larger (> 1 cm); subcutaneous bruises that change from red/blue —> blue/green —> gold/brown as Hb broken down to hemosiderin
20
Q
Virchow’s Triad
A
- 1- Endothelial Injury
- Ulcerated atherosclerotic plaques, trauma, inflammation/vasculitis, stress of hypertension, toxic hypercholesterolemia, smoking toxins
- Previous MI
- 2- Abnormal Blood Flow
- Turbulence from plaques
- Stasis from a fib (decreased contractions), aneurisms, arterial dilations,
- 3- Hypercoagulability
- Genetic
- Factor V Leiden mutation
- Prothrombin gene mutation
- Rare - deficiencies in antithrombin III, protein C or protein S
- Acquired
- Antiphospholipid Antibody Syndrome
- Heparin Induced Thrombocytopenia-
- Secondary hypercoagulable conditions: immobility, oral contraceptives, hormone replacement therapy, obesity, pregnancy, trauma, post-partum period
- Genetic
21
Q
Types of Shock
A
- Cardiogenic - low cardiac output due to pump failure
- Hypovolemic - low cardiac output due to loss of blood or plasma volume (usually must lose 20%)
- Septic - systemic vasodilation, blood pooling, systemic immune rxn, microvascular thrombosis and end organ damage
- Others - neurogenic (SC injury) or anaphylactic (systemic allergic reaction)
22
Q
Cardiogenic Shock
A
- Causes: MI, cardiac tamponade, pulmonary embolus, ventricular arrhythmia
- Treatment: Ionotropes to increase contractility or pressers; surgical bypass or percutaneous coronary intervention
23
Q
Hypovolemic Shock
A
- Causes: burns, trauma, exsanguination, insanguination
- Treatment: fluids and blood (if respond to this then confirms diagnosis of this type of shock); surgery to stop bleeding
24
Q
Septic Shock
A
- Causes: bacterial or fungal infections
- Treatments: ANTIBIOTICS; fluids, insulin, corticosteroids for adrenal damage; treat DIC
25
Q
4 Main Events of Septic Shock
A
- 1- Vascular
- Vasodilation and inc permeability due to cytokines, dec perfusion (esp at micro vessels —> contributes to clot formation)
- 2- Thrombotic
- Complement activated and activates endothelial cells, microvascular thrombosis (DIC); endotoxins from bacteria —> pro-clot
- DIC - clot formation and fibrinolysis at same time so both clots and bleeding in arterioles and capillaries deep in tissues
- 3- Immunosuppressive
- Hyper immune state then causes counter regulatory measures
- 4- Metabolic
- Insulin resistance, hyperglycemia, gluconeogenesis
- Waterhouse-Friderichsen Syndrome- adrenal gland necrosis or hemorrhage into adrenal gland
26
Q
ARDS
A
- ARDS (Adult Resp Distress Syndrome) - sometimes seen due to dec cardiac output, vascular permeability and endothelial damage in lungs —> pulmonary edema and acute damage (SEE HYALINE MEMBRANE FORMATION)
- Edema damages alveoli so covered in membranous coating and no O2 gets to the area
27
Q
3 Stages of Shock
A
- 1- Nonprogressive
- Redistribution to conserve vital organs; so less flow to extremities (cold and pale) as well as inc in cardiac output to compensate
- 2- Progressive
- Lactic acidosis due to anaerobic metabolism; sign of hypoxia/anoxia (tissues not getting oxygen)
- Lactic acidosis —> lower pH which blunts vasomotor response and worsens hypoxia and CO
- 3- Irreversible
- Organs start to shut down and stop functioning
- Free radicals and NO accumulate —> dec contractility of heart
- Ischemic bowel —> further bacteremia
- Renal shut down as tubular necrosis starts
28
Q
SIRS
Sepsis
Severe Sepsis
Multi-Organ Failure
A
- SIRS- systemic inflammatory response syndrome - non-specific response to infection or non-infectious inflammatory response; Must have 2+ of following:
- Fever more than 38 deg C or less than 36 deg C
- HR > 90 bpm
- Resp rate > 20/min or PaCO2 < 32 mmHg
- WBC > 12,000 or <4,000 - Sepsis - SIRS + source of infection
- Severe Sepsis - sepsis w/ organ dysfunction, hypotension or hypoperfusion
- Multi-organ dysfunction syndrome (multi-organ failure) - septic shock w/ 2+ organs failing
29
Q
Active v Passive Congestion
A
- Hypermia - active congestion - engorged w/ blood due to arterial dilation
- Passive congestion - reduction in blood flowing out of the tissue due to back up
- Ex) Nutmeg liver due to upstream L heart failure and pulmonary edema
- Ex) Back up in spleen and liver “congestive hepatosplenomegaly
30
Q
5 Causes of Edema
A
- 1- Inc hydrostatic pressure (too much pressure inside vessel forces fluid out)
- Ex - deep vein thrombosis causing blockage
- Results in transudate (protein poor)
- 2- Dec plasma osmotic pressure
- Dec in albumin in plasma —> can no longer keep fluid from leaking out
- Dec b/c less synthesized by liver or protein lost in urine if nephrotic syndrome
- Results in transudate (protein poor)
- 3- Sodium Retention
- Dec in renal blood flow causes kidney to retain Na+ and water via renin-angiotensin
- 4- Inflammation (inc blood vessel permeability) - local or generalized
- Results in exudate - protein rich pus
- 5- Lymphatic Obstruction
- Due to tumor, inflammation, surgery, radiation or scar; also parasitic infection
- Also results in exudate
31
Q
Vegetations
A
non-bacterial but can become infected; can also be autoimmune or seen in cancer patients w/ inc hypercoagualbility
32
Q
4 Fates of Thrombus
A
- 1- Dissolution - rapid shrinkage and dissolution due to fibrinolysis
- 2- Propagation - further accumulation of fibrin and platelets
- 3- Embolization - parts of clot break-off and dislodge —> end up in another part of vasculature
- 4- Organization - recanalization; ingrowth of fibroblasts, smooth muscle cells, endothelial cells; form new lumen; flattens into a scar-like clump that narrows vessel
33
Q
5 Types of Emboli
A
- Thromboemboli - most common; systemic thromboembolic most commonly travel from heart to legs or brain
- Fat embolism - commonly from long bone fractures/trauma; clinically silent OR sudden dyspnea, tachypnea, tachycardia, restlessness, irritability, anemia, thrombocytopenia
- Air embolism - air in IV infusion, scuba diving, sudden change in atmospheric pressure, chest wall injury, back surgery in prone position (need 100 mL for effect)
- Amniotic fluid embolism - tears in placental membrane; squamous cells, lanuga hair, mucin or vernix cases fat travels from uterus —> lung (dyspnea, cyanosis, shock)
- Paradoxical embolism - when clot travels from venous to arterial circulation thru patent foramen ovale, arterial septal defect, patent ductus arteriosus
34
Q
4 Determinants of Likelihood of Infarction
A
- Organ’s vulnerability to hypoxia (ex- neurons very vulnerable- die after 4 min ischemia)
- Rate of development of vascular occlusion (faster the occlusion occurs = less time to compensate)
- Does organ have dual blood supply
- Oxygen content of blood (may have co-morbidity hat dec O2 content - inc chance of infarct)
35
Q
2 Types of Infarction & Which Organs?
A
- White- pale/anemic; normally if organ only has one source of blood flow (brain)
- Red- hemorrhagic; if organ still gets blood from other sources (lung, liver, transverse colon, intestine)
36
Q
6 Types of Necrosis
A
- Coagulative
- Most common; architecture of dead tissue initially preserved; usual elicits acute inflammatory response (neutrophilic response peaks in 1-2 days then macrophages and fibroblasts)
- Liquefactive
- Dead tissue is digested and transformed into liquid mass (usually pus); lose architecture; common in brain
- Gangrenous
- Distinct form of coagulative; shrinkage and blackening; usually extremity or gallbladder; if infection on top of it then dry gangrene —> wet gangrene; if Chlostridium infection —> gas gangrene; treat w. surgical removal
- Saponification
- Fat necrosis; breakdown —> fatty acids which react w/ calcium to form chalky white soap-like material; appears bright white on histo image; usually in fat of extremities, pancreas (pancreatitis) and omentum
- Can occur as a result of direct injury; usually accompanied by hemorrhage and destruction of surrounding its; may also get fat embolism (usually MVAs or pedestrian struck by motor vehicle)
- Caseous
- Associated w/ tuberculosis infection; granuloma look like cheese (necrotic centers and inflammatory borders)
- Fibrnoid
- In autoimmune reactions when antigen-antibody complexes build up in blood vessel walls
37
Q
Hemosiderin
A
- By-product of iron metabolism; seen normally in certain cell types OR if iron overload
- Normal circumstances- normal red cell breakdown; seen in mono-nuclear phagocytes of bone marrow, liver (Kipper cells) and spleen
- Pathological - localized iron overload (seen in hemorrhage in form of bruises) OR systemic iron overload (ex- hereditary hemochromatosis)
- Left behind by dead cells (not broken down by macrophages)
- Gold/brown granular pigment (seen in images) OR can stain iron and it appears blue
