Approach to bleeding and thrombosis Flashcards
What is defined as the arrest of bleeding?
hemostasis
What are the components of hemostasis?
- vasculature (endothelial cells and subendothelial matrix)
- platelets
- blood proteins (clotting factors)
What is the sequence of events of hemostasis?
- vascular injursy leads to vasoconstriction
- formation of a platelet plug (primary hemostasis)
- tissue factor activates coagulation cascade
- formation of a blood clot (secondary hemostasis)
- clot retraction and clot dissolution
What are vascular spasms triggered by?
- direct injury to vascular smooth mm
- chemicals released by endothelial cells and platelets
- pain reflexes
Pertaining to step 1 of hemostasis, vascular spasms:
- vessels respond to injury with (…)
- most effective in what type of blood vessels?
- can significantly reduce (…) until other mechanisms kick in
- vasoconstriction
- smaller blood vessels
- blood flow
Pertaining to step 2 platelet plug formation of hemostasis:
- platelets stick to (…) that are exposed when vessels become damaged
- platelets do not stick to intact vessel walls because (…) is not exposed
- (…) and (…) which are secreted by endothelial cells act to prevent platelet sticking, therefore, keeps the platelets away
- collagen fibers
- collagen
- prostacyclins and nitric oxide
What helps stabilize platelet-collagen adhesion?
Where is this found?
- Von Willebrand Factor (VWF)
- on platelets
Sometimes there can be too much collagen present which increases the risk of what?
clotting
Pertaining to step 2 platelet plug formation of hemostasis:
- What happens to platelets when they are released?
- Platelet plug formation is known as a (…) cycle; explain this
- Platelet plugs are fine for (…), but (…) in vessels need additional steps
- platelets swell, become spiked and sticky, and release chemical messengers
- positive feedback cycle; as more platelets stick, they release more chemicals, which cause more platelets to stick and release more chemicals
- small vessel tears; larger breaks
What are the chemical messengers that platelets release when they are activated?
- ADP
- Serotonin
- thromboxane A2
Which chemical messenger released by platelets causes more platelets to stick and release their contents, increasing platelet aggregation?
ADP
Which chemical messenger(s) released by platelets enhances vascular spasm and platelet aggregation?
serotonin and thromboxane A2
Pertaining to step 3 coagulation of hemostasis:
- Coagulation (blood clotting) reinforces (…) with (…)
- Blood clots are effective in sealing (…) vessel breaks
- Blood is transformed from (…) to (…)
- Series of reactions use (…), mostly (…)
- Coagulation occurs in (…) phases
- platelet plug with fibrin threads
- larger vesse breaks
- liquid to gel
- clotting factors (procoagulants), mostly plasma proteins
- three phases
- What are the numbers of clotting factors?
- Vitamin K is needed to synthesize four factors, (…), along with protein (…) and (…)
- I to XIII (no VI); numbered in order of discovery
- II, VII, IX, X; protein C and S
What are the 2 different pathways of coagulation?
- intrinsic pathway
- extrinsic pathway
Which coagulation pathway is this describing:
- vessel endothelium ruptures, exposing underlying tissues; platelets clind and their surfaces provide sites for mobilization of factors?
intrinsic pathway
Which coagulation pathway is this describing:
- tissue cell trauma exposes blood to tissue factor (TF) (occurs extrinsic to the vascular wall)
extrinsic pathway
- What is the first clotting factor that activates the coagulation cascade in the intrinsic pathway?
- Which clotting factors follow this?
- clotting factor XII
- XI, IX, VIII comes in and activates, IX/VIII complex is formed
What is the pathway of coagulation in the extrinsic pathway?
- begins with tissue factor
- Ca2+ (considered facor IV) comes in
- factor VII comes in, is activated, then communicates with the intrinsic pathway
- TF/VII complex is formed
- Which factor is where the common coagulation pathway begins?
- What activates this factor?
- factor X
- IX/VIII complex + TF/VII complex
What does phase 2 of coagulation consist of?
prothrombin (factor II) converts to thrombin (IIa)
What does phase 3 of coagulation consist of?
fibrinogen (factor I) converts to fibrin and with the help of Ca2+ and XIII, a cross-linked fibrin mesh is formed
What is activated when tissue trauma occurs?
extrinsic pathway
What is activated under conditions such as stress, anxiety, or fear, and in the abscence of external tissue injury?
intrinsic pathway
In stage one of the coagulation cascade, either the extrinsic or intrinsic pathway ends with the formation of (…)
prothrombin-converting factor
In stage two of the coagulation cascade, prothrombin-converting factor begins a series of chemical interactions which slowly converts (…) to (…)
- prothrombin
- thrombin
In stage 3 of the coagulation cascade, What happens?
fibrinogen interacts with thrombin to form fibrin
What all collect at the site of injury to complete thrombosis development?
erythrocytes, phagocytes, and microorganisms
What time is used to evaluate how well the intrinsic pathway of coagulation is working?
activated partial thromboplastin time (aPTT)
What is the typical time frame of aPTT?
25-39 seconds
The pTT is used to evaluate what factors?
- XII
- XI
- IX
- VIII
- X
- V
- II (prothrombin)
- I (fibrinogen)
What time is used to evaluate how well the extrinsic coagulation pathway is working?
prothrombin time
What is the typical time frame for PT?
12 seconds
The PT test evaluates which clotting factors?
- VII
- X
- V
- II
- I
What are most clotting factors made?
the liver
- Which clotting factor is involved in the common pathway and is converted to fibrin?
- What is the factor name?
- Where is this made?
- I
- fibrinogen
- liver
- Which clotting factor is involved in the common pathway and is converted to thrombin (converts fibrinogen to fibrin)?
- What is the factor name?
- Where is this made?
- II
- prothrombin
- liver
- Which clotting factor activates the extrinsic pathway?
- What is the name of this factor?
- Where is this made?
- III
- tissue factor (TF)
- tissue cells
- Which clotting factor is needed for all stages of the coagulation process as it is always present?
- What is the name of this factor?
- Where is it made?
- IV
- Calcium ions (Ca2+)
- plasma
- Which clotting factor functions in the common pathway?
- Where is this made?
- V
- liver, platelets
- Which clotting factor functions both in the extrinsic and extrinsic pathways?
- Where is this made?
- VII
- liver
- Which clotting factor is involved in the intrinsic pathway and a deficiency results in hemophilia A?
- Where is this made?
- VIII
- liver, lung capillaries
- Which clotting factor is involved in the intrinsic pathway and a deficiency results in hemophilia B?
- Where is this made?
- IX
- liver
- Which clotting factor marks the beginning of the common pathway?
- Where is this made?
- X
- liver
- Which clotting factor functions in the intrinsic pathway and a deficiency results in hemophilia C?
- Where is this made?
- XI
- liver
- Which clotting factor is involved in the intrinsic pathway and activates plasmin, initiates clotting in vitro; activation initiates inflammation?
- Where is this made?
- XII
- liver
- Which clotting factor cross-links fibrin, forming a strong stable clot?
- Where is this made?
- XIII
- liver, bone marrow
What are the 2 major types of hemostasis disorders?
- thromboembolic disorders
- bleeding disorders
Which hemostasis disorder results in an undesirable clot formation?
thromboembolic disorders
Which hemostasis disorder results in abnormalities that prevent normal clot formation?
bleeding disorders
What hemostasis disorder involves both thromboembolic disorders and bleeding disorders?
disseminated intravascular coagulation (DIC)
What is required for hemostasis?
- healthy endothelium
- functioning platelets
- von willebrand factor
- adequate clotting/anticlotting facotrs
What is the general presentation of bleeding disorders?
- excessive or repetitive bleeding
- bleeding at unusual sites: petechia, bruising, mucosal bleeding; hemarthroses and deep tissue hematomas; purpura
What are the sites of bleeding in the skin for platelet-vascular disorders vs coagulation factor deficiency?
- platelet-vascular disorders: superficial surfaces
- coagulation factor deficiency: deep tissues
What may be present in the mucous membranes in platelet-vascular disorders vs coagulation factor deficiencies?
- platelet-vascular disorder: petechiae, ecchymoses
- coagulation factor deficiency: hematomas
What are some other sites of bleeding besides the skin and mucous membranes in platelet-vascular disorders vs coagulation factor deficiencies?
- platelet-vascular disorder: common in oral, nasal, GI, and GU
- coagulation factor deficiency: rare
Where is the onset of bleeding in platelet-vascular disorders vs coagulation factor deficiencies?
- platelet-vascular: rare
- coagulation factor deficiencies: joint, muscle, retroperitoneal
What are some clinical examples of bleeding d/t platelet vascular disorders vs coagulation factor deficiency?
- platelet vascular disorders: spontaneous or immediately after trauma
- coagulation factor deficiency: delayed after trauma
What are some diagnostic studies you can order for hemostasis disorders?
- CBC
- PT/INR/aPTT
- TT
- metabolic panel
- D-dimer
- inhibitor screen
- lupus anticoagulant/other coagulation factor inhibitors
- vWF
- bleeding time
What is used in VW disease that determines cellular changes?
platelet functional analysis
What diagnostic test is reported as INR and evaluated the clotting pathway?
PT (protime)
What is a normal INR?
1
If a patient is going into surgery, what always needs to be ordered?
- coagulation panel (PT, INR, aPTT)
- If either PT/PTT is prolonged, what can be ordered that measures the rate of fibrinogen conversion to fibrin, in the presence of thrombin?
- What does this assess?
- TT (thrombin time)
- common pathway; sees if theres is a problem below the extrinsic/intrinsic pathways
What hemostasis disorder diagnostic test assesses the kidney and liver function?
metabolic panel
What is used to assess/ID thrombosis in suspected clotting disorders?
D-dimer
What disorders can you use the D-dimer test for?
- TTP
- HUS
- DIC
- HELLP
- HIT
What is the issue with the D-dimer?
good sensitivity, poor specificity
What test is where there is a 1 to 1 mix to assess for factor deficiency, so patients are given clotting factors to see if PTT/PT goes back to normal; if no, something is inhibiting the factors
inhibitor screen
What tests are given to assess if there is a clotting factor issue or if something is inhibiting the factors from working?
- inhibitor screen
- lupus anticoagulant/other coagulation factor inhibitors
What diagnostic test assesses platelet function by finding how long it takes for a patient to stop bleeding?
bleeding time
What are examples of what could be wrong is PT is elevated, but aPTT is normal?
- liver disease
- decrease in vitamin K
- decrease in factor VII
- anticoagulation drug therapy
What are examples of what could be wrong if PT is normal but aPTT is elevated?
- mainly injury related
- decreased factor VIII, IX, or XI (severe factor XI deficiency)
- von willebrand disease
- hemophilia A or B
What are examples of what could be wrong if both PT and aPTT are extended?
- decrease in factor I, II, V, or X
- severe liver disease
- DIC
(common factor deficiency)
What could be wrong is PT and aPTT are extended but PLT (platelets) are low?
- DIC
- liver disease
- lupus anticoagulants
- The finding of a prolonged PT and/or aPTT indicates either a deficiency in (…) or (…), usually an (…) directed at one or more components of the coagulation system
- These two possibilities can be distinguished by performing a (…), which involves a 1 to 1 mix of the patients plasma and normal plasma
- If it corrects, what should you do?
- If it doesn’t correct, what should you do?
- one or more coagulation factors or the presence of an inhibitor, usually an anitbiody
- inhibitor screen
- find which clotting factor is wrong/not working
- find what is inhibiting the clotting factors
