HEMOSTASIS SURGICAL BLEEDING TRANSFUSIONS Flashcards
hemostatic process
- Process involves interaction between blood vessel wall, platelets, and coagulation proteins
- When systems coordinate, a clot is laid down initially to stop bleeding, followed by eventual clot lysis and tissue remodeling.
- Abnormal bleeding can result from diminished thrombin generation (eg, due to factor VIII deficiency) or enhanced clot lysis (eg, due to alpha-2-antiplasmin deficiency).
- Conversely, excessive production of thrombin can lead to thrombosis
⦁ decreased clot formation or increased clot breakdown –> abnormal bleeding
phases of hemostasis
1) endothelial injury & formation of platelet plug
2) clotting process by coagulation cascade
3) termination of clotting by antithrombotic mechanisms (plasmin, antithrombin, protein S & protein C - degrade factors 5a & 8a)
4) Removal of clot by fibrinolysis
protein S & protein C
aid in prevention of clotting cascade
degrade factors 5a & 8a
factor 5 leiden
excessive production of factor 5 –> excessive clot formation
ADP function
adenosine diphosphate
released from platelets upon platelet activation and functions to recruit additional platelets and amplify platelet aggregation
ADP is released from platelets when stimulated –> recruits more platelets to the site of injury
Plavix / Clopidogrel blocks platelet activation by ADP
PLATELET ACTIVATION
After injury to vessel wall
⦁ Vasoconstriction for about 60 seconds
⦁ Next platelets adhere to site of vascular injury; physiologic platelet stimuli – Collagen and thrombin (further activates platelets), ADP.
⦁ ADP adenosine diphosphate is released from platelets upon platelet activation and functions to recruit additional platelets and amplify platelet aggregation
(this is where Plavix works - prevents platelets from being able to signal to one another for aggregation)
PLATELET ADHESION
After activation platelets undergo significant shape changes that make the platelets extremely adhesive.
Platelet adhesion is primarily mediated by the binding of platelet surface receptor GPIb/IX/V complex to von Willebrand factor (VWF) in the subendothelial matrix
Von Willebrand Factor (VWF)
lines vessels; acts as bridging molecule at sites of vascular injury for platelet adhesion; also acts as a carrier protein for factor 8 (needed for fibrin formation)
von Willebrand disease
deficient or abnormal function of VWF = most common of inherited bleeding disorders;
platelets can’t adhere to vessel, and factor 8 gets broken down faster and can become deficient too (leading to hemophilia A)
PLATELET AGGREGATION
Results in platelet-platelet cohesion.
Results in both exposure of and conformational changes in the GPIIb/IIIa receptor on the platelet surface, leading to binding of both immobilized VWF and fibrinogen
fibrinogen is secreted from
platelets (but still has to be converted to fibrin…from thrombin)
platelets contain 2 types of granules
alpha & dense
platelets secrete substances from their granules (alpha & dense granules)
ADP (platelet recruitment / activation)
growth factor - helps with tissue repair
fibrinogen - helps solidify platelet aggregation
tissue factor (factor 3) is also known as
thromboplastin
coagulation pathway summary
- Various coagulation factors are activated to generate fibrin
- Extrinsic Pathway
⦁ begins with thromboplastin (= tissue factor = factor 3)
⦁ thromboplastin / TF / factor 3 -> activates factor 7 to 7a -> activates factor 10 to 10a - Intrinsic Pathway
⦁ Requires factors 12, 11, 9 and 8 to convert factor 10 to 10a - Common Pathway
⦁ involves factor 10, 5, 2 (prothrombin) and 1 (fibrinogen)
⦁ factor 13 = fibrin stabilizing factor; creates crosslinks to hold fibrin strands together
thrombin (2a) then activates which clotting factors
5, 7, 8, 11, 13
which electrolyte is ESSENTIAL to the clotting cascade
CALCIUM
PTT = \_\_\_\_\_\_\_\_\_\_ pathway PT = \_\_\_\_\_\_\_\_\_\_\_ pathway
PTT = intrinsic
PT = extrinsic
intrinsic pathway is activated by
extrinsic pathway is activated by
Intrinsic pathway is activated by damage directly to the blood vessel and the exposure of collagen to the circulating platelets within the blood.
The extrinsic pathway is activated by many things.
Intrinsic pathway = think injury*
in order for factor 9a to activate factor 10, need
factor 8!
damage / collagen exposure activates factor 12 -> 12a
12a activates 11 -> 11a
11a activates 9 -> 9a
9a activates 8 -> 8a
9a + 8a together activate factor 10 -> 10a
INTRINSIC VS EXTRINSIC PATHWAY
INTRINSIC PATHWAY
⦁ damage / collagen exposure activates factor 12 -> 12a
⦁ 12a activates 11 -> 11a
⦁ 11a activates 9 -> 9a
⦁ 9a activates 8 -> 8a
⦁ 9a + 8a together activate factor 10 -> 10a
EXTRINSIC PATHWAY
⦁ damage / exposure of tissue factor (3) = activates 3 -> 3a
⦁ 3a activates 7 -> 7a
⦁ 7a activates 10 -> 10a
factors 1-7 = also called….
⦁ Factor I – Fibrinogen ⦁ Factor II – Prothrombin ⦁ Factor III – Tissue factor ⦁ Factor IV – Calcium ⦁ Factor V – Labile factor ⦁ Factor VI – not used anymore ⦁ Factor VII – proconvertin
factor deficiencies
Factor 8 – Hemophilia A Factor 9 – Hemophilia B = Christmas Factor 10 - Stuart-Prower Factor 11- Hemophilia C Factor 12 - Hageman factor deficiency Factor 13 - fibrin stabilizing factor
rarest factor deficiency
factor 13 deficiency
clot forms, but breaks down quickly, because factor 13 is what stabilizes the fibrin to hold platelets together
normal platelet count
140,000 - 400,000
H&P for bleeding issues
- HISTORY = most important step
⦁ ask about meds: OTC, ASA, Clopidogrel (Plavix), Warfarin (Coumadin) - ASA, plavix = antiplatelet = used to prevent clots in arteries
- Warfarin (& heparin) = anticoagulant = used to slow clotting in veins (DVT)
- PE = look for signs of a bleeding disorder
evaluation (labs) for bleeding
⦁ platelet count
⦁ PT (prothrombin time) = extrinsic pathway
⦁ PTT (partial thromboplastin time) = intrinsic pathway
⦁ bleeding time
⦁ thrombin time
PLATELET COUNT
verifies that patient has an adequate number of platelets available in circulation; if abnormal = can order a blood smear to look at the platelets under a microscope
normal = 140,000 - 400,000
PROTHROMBIN TIME (PT)
- evaluates the extrinsic pathway
- measures the ability of the blood to form a stable thrombi
- evaluates factors 7, 10, 5, prothrombin (2) and fibrinogen (1)
- most common use = MONITORING WARFARIN
- PT is reported with INR (international normalized ratio) = ratio of a patient’s prothrombin time to a normal (control) sample
most common use for PT
monitoring warfarin therapy
why is PTT normal in a patient with factor 7 deficiency
because PTT measures the intrinsic pathway, and factor 7 is in the extrinsic pathway (PT)
most common use for PTT
evaluate UNFRACTIONATED HEPARIN therapy
PARTIAL THROMBOPLASTIN TIME (PTT)
Intrinsic pathway
- evaluates the adequacy of factors 12, 11, 10, 9, 8, 5, 2 (prothrombin), 1 (fibrinogen)
- most commonly used to evaluate UNFRACTIONATED HEPARIN therapy
- PTT = normal in patients with factor 7 deficiency…because PTT measures the intrinsic pathway, and factor 7 is in the extrinsic pathway (PT)
BLEEDING TIME
- Two incisions with lancet on the forearm
- Time from injury to cessation of bleeding from both wounds is measured
- Normal range is 5-10 minutes
- Prolonged time may indicate;
⦁ Thrombocytopenia (low platelets)
⦁ Medication (ASA) - (anti-platelet- prevents coagulation)
⦁ Von Willebrand disease (factor needed for platelet to adhere to vessel & acts as carrier protein for factor 8
THROMBIN TIME
- Evaluates fibrinogen-to-fibrin conversion with an external source of thrombin
- Prolongation may indicate: ⦁ Low fibrinogen levels ⦁ Abnormal fibrinogen ⦁ Fibrin and fibrinogen split products ⦁ Heparin (anti-coagulant = binds to antithrombin and intensifies action - inhibits thrombin activation & inhibits factor 10 from converting to 10a)
heparin MOA
anti-coagulant = binds to antithrombin and intensifies action - inhibits thrombin activation & inhibits factor 10 from converting to 10a
reversed with protamine sulfate
warfarin MOA
inhibits synthesis of vitamin K - calcium dependent clotting factors (2, 7, 9, 10) - ***7 = warfarin = think extrinsic
warfarin = reversed with vitamin K
PT (extrinsic) & PTT (intrinsic) meet at factor
10
X marks the spot!
time it takes to convert fibrinogen to fibrin
thrombin time
common pathway factors
10 / 5 / 2 / 1
If PT and PTT are both prolonged = have factor deficiency in common pathway (unless have multiple factor deficiencies - in both extrinsic & intrinsic pathway)
if only PT is prolonged = factor ______ deficiency
7
if only PTT is prolonged = could have deficiencies in which factors
8, 9, 11, 12
surgical bleeding
pre-existing hemostatic defects
⦁ Congenital bleeding disorders (hemophilia / factor deficiencies / VWD)
⦁ Acquired bleeding disorders (ex: Cirrhosis / hepatitis - can’t properly synthesize clotting factors, Vitamin K deficiency - needed to synthesize factors 2, 7, 9, 10)
⦁ Medication-Associated bleeding - aspirin, plavix, heparin, warfarin, etc.
PT and PTT and platelet function for VWD
normal PT
prolonged PTT
abnormal platelet function
von Willebrand disease
- 1% of US population
- Pathophys = reduced factor 8 activity & von willebrand activity (binding of platelet to VWF on endothelial surface
- Site of bleeding = mucocutaneous (nose bleeds, heavy menstruation, gums, etc)
- Autosomal dominant;
affects males & females equally
- have normal PT, but prolonged PTT (affects factor 8 - intrinsic), and have abnormal platelet function (not able to bind to VWF)
treatment for VWD
o cryoprecipitate infusions of VWF & VIII (can be used with platelet transfusions too)
o DDAVP (desmopressin) = will retain water; MOA = promotes the release of VWF from cell storage sites. Tachyphylaxis occurs after repeated DDAVP (rapid decrease in response to drug with repeated use) - therefore doses of DDAVP are usually limited to once daily after the first day, and only for a total of 3-5 days
- also monitor for hyponatremia (too much volume –> washed out)
DDAVP for tx of VWD - limited to 3-5 days because of
tachyphylaxis = diminished response with repeated use
sites of bleeding with VWD
mucocutaneous skin
sites of bleeding with hemophilia A
joints & intramuscular
hemophilia A labs
normal PT
prolonged PTT
normal platelet function
(same as VWD except for platelet function)
HEMOPHILIA A
- 25/100,000 in US
- Pathophys = reduced or absent factor 8
- Site of bleeding = joints & intramuscular
- Only males
- Labs = normal PT, prolonged PTT, normal platelet function
- TREATMENT = purified factor 8 products; can give DDAVP for mild disease
HEMOPHILIA A TREATMENT
purified factor 8 products
can give DDAVP for mild disease
acquired bleeding disorders
⦁ Advanced Liver Disease ⦁ Anticoagulation therapy ⦁ Acquired thrombocytopenia ⦁ Platelet-inhibiting drugs ⦁ Uremia
obstructive jaundice and cirrhosis respond well to
vitamin K
LIVER DISEASE = common cause of acquired bleeding disorder
Common cause
Inability to synthesize proteins leads to decreased levels of prothrombin and factors V,VII, and X
Obstructive jaundice and Cirrhosis may lead to clotting factor deficiencies = Respond well to vitamin K
vitamin K and _________ act on the same factors
CALCIUM
warfarin inhibits vitamin K dependent factors = 2, 7, 9, 10
ANTICOAGULATION THERAPY = another cause of acquired bleeding disorder
- Warfarin (Coumadin)
⦁ Depression of clotting factors 2, 7, 9, 10
⦁ Can be reversed with FFP or Vitamin K in an emergency - Heparin
⦁ Increased speed of antithrombin III - binds to and neutralizes factors 12, 11, 10, 9, and thrombin (2)
⦁ Prolongs PTT and Thrombin time
⦁ Reversed with Promatine Sulfate
Warfarin inhibits which factors
2, 7, 9, 10
heparin inhibits which factors
2, 9, 10, 11, 12 (intrinsic)
which is why heparin prolongs PTT and thrombin time
ACQUIRED THROMBOCYTOPENIA = cause of acquired bleeding disorder
- 3 mechanisms
⦁ Decreased platelet production in bone marrow
⦁ Increased destruction of platelets in peripheral blood
⦁ Splenic pooling in enlarged spleen
ANTI-PLATELET THERAPY = acquired bleeding disorder
- ASA = should stop 1 week before surgery
- Plavix (Clopidogrel) = should be stopped 7-10 days before surgery
- NSAIDS
UREMIA - acquired bleeding disorder
- Platelet dysfunction
- Patients who are bleeding and need surgery require dialysis to correct platelet dysfunction
uremia = urea in blood due to kidney dysfunction
intraoperative bleeding is controlled with
⦁ gelfoam - dissolvable
⦁ surgicel - provides a surface for platelets to grab onto to form clots
⦁ floseal - liquid that contains thrombin to help form clots
⦁ tisseel - liquid sealant with fibrin in it
⦁ Avitene Collagen = packing or in sprinkle form = collagen based - enhances platelet aggregation
⦁ good team work
Avitene & Gel-foam are used often
50% of post-op bleeding is caused by
poor hemostasis during surgery
other causes of post-op bleeding
⦁ Residual heparin
⦁ Shock
⦁ Altered liver function
3 main categories of post-op bleeding classifications
⦁ primary bleeding (bleeding during surgery)
⦁ reactive bleeding (bleeding after surgery; ligature slips or missed vessel, or clot is displaced)
⦁ secondary bleeding (occurs 7-10 days post-op; often due to erosion of a vessel from a spreading infection or rubbing clip, or contaminated wounds)
primary = think intra-operative bleeding reactionary = think ligature slips or missed vessel secondary = think erosion
secondary bleeding is often due to
erosion of a vessel from spreading infection
DIC
characterized by intravascular coagulation & thrombosis that is diffuse instead of localized at the site of injury
- results in systemic deposition of platelet-fibrin microthrombi that cause diffuse tissue injury
- thrombosis & hemorrhage; thrombosis first, then use up all clotting factors and bleed
ETIOLOGY OF DIC
- release of tissue debris into bloodstream after trauma, infection or obstetric catastrophe
- extensive endothelial damage to vascular wall
- hypotension
- operations with large blood loss (prostate, lung, malignant tumors)
diagnosis of DIC
- diagnosed by diminished levels of coagulation factors & platelets
- Labs ⦁ prolonged PT & PTT ⦁ hypofibrinogenemia ⦁ thrombocytopenia ⦁ presence of fibrin & fibrinogen products
TREATMENT OF DIC
**Most important = remove the precipitating factors
- Severe DIC
⦁ cryoprecipitate = best method to replace fibrinogen loss
⦁ platelet transfusion may be necessary
⦁ FFP helps replace other deficits (factors)
most common cause of fatal transfusion reactions
ABO incompatibilities
BLOOD TYPING & CROSS-MATCHING
- only 2 groups have immunologic relevance
⦁ ABO group
⦁ Rhesus group
- Antigens ⦁ Type A = only has A antigen ⦁ Type B = only has B antigen ⦁ Type AB = has both A & B antigen ⦁ Type O = has neither antigen
***ABO incompatibilities = most common cause of fatal transfusion reactions
what blood type can give and receive what blood types
Type A = can give blood to A & AB, can receive blood from A & O
Type B = can give blood to B & AB, can receive blood from B & O
Type AB = can give blood to AB, can receive blood from A, B, AB, O
Type O = can give blood to A, B, AB, O, can receive blood from O
which antigen is tested for Rhesus
D
- Only the D antigen is tested
⦁ D antigen present on RBC = Rh+
⦁ no D antigen present on RBC = Rh-
1 unit of PRBCs into an average 70kg person raises the
hematocrit by 3% and hemoglobin by 1g/dL
TRANSFUSION OF RBCs
- 5 types ⦁ whole blood ⦁ packed RBCs ⦁ washed RBCs ⦁ Leukoreduced RBCs (less reactions) ⦁ Divided or Pediatric unit RBCs
- RBC transfusions = used for massive transfusions & life-saving transfusions
- The decision to transfuse RBCs is multifactorial & individualized
⦁ reason for anemia
⦁ degree & acuity/chronicity of anemia
⦁ underlying medical condition
⦁ anticipated future transfusions
⦁ hemodynamic instability
if H&H is < 10 & 30 = need to monitor
- 1 unit of PRBCs into an average 70kg person raises the hematocrit by 3% and hemoglobin by 1g/dL
have less reactions with which type of RBC transfusion
leukoreduced RBCs
FFP
FFP = platelet-poor plasma removed from whole blood FFP = no platelets, RBCs or Leukocytes
- Indications
⦁ evidence of coagulation factor deficiency with clinical bleeding
⦁ need for invasive procedure
FFP contains clotting factors; no platelets, RBCs or leukocytes
- can give to reverse coumadin effects (warfarin - or can give vitamin K)
PLATELET TRANSFUSION
- indicated for patients with thrombocytopenia due to platelet dysfunction
- Labs
⦁ increased bleeding time
⦁ whole blood platelet function testing - The transfusion of 6 platelets (bags) = raises platelet count by 50,000 - 100,000
- need to give platelet transfusion if platelet count < 50k
transfusion complications
- metabolic derangements
- immunologic reactions
- infection complications
- volume overload
- pulmonary complications
metabolic derangements with transfusions
- seen with large volumes or older blood products
⦁ hypocalcemia
⦁ hyper and hypokalemia
⦁ hypothermia
⦁ hypocalcemia - seen with rapid transfusion; have muscle tremors, ST prolongation, delayed T waves
⦁ hyper and hypokalemia - hyperkalemia = found in units of blood frozen > 35 days. After transfusion, infused potassium is taken up by RBCs, causing hypokalemia
⦁ hypothermia - multiple transfusions need to be through a fluid warmer
hypocalcemia from transfusions is seen with
rapid transfusion
presents with
- muscle tremors
- prolongation of ST segment
- delayed T waves
hyper and hypokalemia with transfusions
hyperkalemia = found in units of blood frozen > 35 days.
After transfusion, infused potassium is taken up by RBCs, causing hypokalemia
what 2 signs are linked to hypocalcemia
trousseau’s sign
Chvostek’s sign
Trousseau’s sign (carpal spasm in response to inflating BP cuff above systolic pressure x 3 minutes) &
Chvostek’s sign (twitching of facial muscles in response to tapping over facial nerve) = both linked to hypocalcemia
IMMUNOLOGIC REACTIONS FROM BLOOD TRANSFUSIONS
- febrile reactions
- acute & delayed hemolytic reactions
- thrombocytopenia
- anaphylactic shock
- urticaria
- graft vs host disease
- immune suppression
mild fever = normal, even with typed/crossed/matched blood; no treatment
Febrile reactions (immunologic reaction) to transfusions
most common as a result of antileukocyte antibodies.
Present with fever, chills, tachycardia;
can pretreat with ASA, antipyretics and antihistamines
febrile reactions are most common a result of
antileukocyte antibodies
hemolytic reactions (immunologic reaction) to transfusions
most caused by ABO-mismatched blood.
Present with hot or cold flushing, chest pain, low back pain, fever & hypotension.
Stop transfusion & re-check blood!
hemolytic reactions are most caused by
ABO mismatched blood
graft vs host disease (immunologic reaction) to transfusions
occurs when immunosuppressed patients receive donor leukocytes; Onset of symptoms are delayed = fever, rash, liver dysfunction, diarrhea.
Prevent with leukocyte-reduced red cells or irradiated red cells
bacterial infection from transfusions = most likely from
platelets
infection complications from transfusions
o Bacteria = most likely from platelets
⦁ present with fever, chills, tachycardia, hypotension
o Viruses
⦁ Hep B (1 / 200,000)
⦁ Hep C (1 / 2 million)
⦁ HIV (1 / 2 million)
o Parasites
pulmonary complications from transfusions
- 1/5000 transfusions
- most common with units that contain plasma
- characterized by pulmonary edema after transfusion
- treatment = supportive (may require intubation)
pulmonary complications from transfusions are most common with transfusions that contain
plasma
massive transfusions / complications
- > 10 packed red cells in 24 hours or pt.’s total blood volume in 24 hours, or half pt.’s blood volume in 1 hour
- Complications; ⦁ Dilutional coagulopathy ⦁ Oxygen transport abnormalities ⦁ Electrolyte/Acid-base derangements ⦁ Hypothermia ⦁ Disease transmission ⦁ ARDS
AUTOLOGOUS BLOOD TRANSFUSIONS
- Collection and re-infusion of a patients own blood
- Collection ⦁ Pre-surgical donation ⦁ Intraoperative cell saver (machine that automatically recycles blood during surgery) Reasons ⦁ Fully compatible ⦁ No risk of transmission ⦁ Less dependent on blood bank ⦁ Patients with rare blood types
