Hematology (Strauss) Flashcards
What are the 4 phases of blood clot formation?
- Vascular
- Platelet
- Coagulation
- Fibrinolytic
What is the phase of clot formation where blood vessels contract (collagen in the vessel contracts to stop the bleeding via a local myogenic spasm)?
Vascular phase
What is the phase of clot formation where platelets distort, clump, and stick to form initial platelet plug (will distort due to the action of instigators)?
Platelet phase
What is the phase of clot formation where blood profactors become factor and react to form fibrin (the basis for the clot)?
Coagulation phase
What is the basis for the blood clot?
Fibrin
What is the phase of clot formation where the clot dissolves to allow healing?
Fibrinolytic phase
What is the local autocoid that is released from traumatized tissue how long do they last, and where are they eliminated?
Synthesized in bone marrow by megakaryocytes
1-4 micrometers
7-10 day half-ife
Eliminated by macrophages in the spleen
Can platelets reproduce?
No. They have no nuclei.
Can platelets contract?
Yes. They have throbosethin, actin, and myosin, which are contractile proteins.
Why is a dental extraction the ultimate challenge to the patient’s ability to clot?
Can’t get primary closure.
Why are scaling and root planing potentially devastating if the patient can’t stop bleeding?
Can’t just easily stop the bleeding, plug it, close, etc.
The platelet surface is coated with what to keep them from adhering to normal endothelium but allows them to adhere to damaged cell walls?
Glycoprotein
Platelets have what on the membrane that activates multiple stages of the coagulation process?
- Phospholipids
2. Platelet Factor 3 (PF3)
Why is the half-life of a platelet and important consideration?
Factor in when taking patient off anticoagulation meds
What is released from platelets and endothelial cells to link the platelets with exposed collagen fibers?
Von Willibrand factor
How long until the initial platelet plug occur?
5-12 minutes
Is the platelet plug strong?
No, but it gives you initial stability
What can cause the fibrin clot to be formed?
- Damaged endothelium
2. Factors in the blood
How long does the fibrin clot take to form?
Up to 6-8 hours
How long with the fibrin clot (a scab) stay there?
A few days
Plasminogin becomes plasmin and dissolves what?
Fibrin clots. This is a process that is occurring all the time.
What is an irreversible platelet poison?
Aspirin
How long does the analgesia of aspirin last?
4 hours
For how long does aspirin irreversably poison your platelets?
7 days
What are necessary for platelet aggregation and activation of nearby platelets in order for the number of activated platelets to increase successively?
- ADP
2. Thromboxane A2
Initially, what activates platelets in the area of a wound?
Exposed collagen fibers in damaged vessel walls
What makes the platelet plug, which is loose at first, stronger?
Fibrin threads from coagulation phase interweaving through the platelet plug
What are 2 major parts of the coagulation system?
- Procoagulants
2. Anticoagulants
In normal blood flow, what part of the coagulation system predominates?
Anticoagulants
What are 2 things that start the coagulation process?
Material from damaged vessel walls in blood (things in blood that notice material or damage)
What are 2 ways to get to the formation of prothrombin activator complex in the coagulation cascade?
- Extrinsic pathway
2. Intrinsic pathway
What is the purpose of the prothrombin activator complex in the coagulation cascade?
Convert prothrombin (Factor II) to Thrombin (Factor IIa)
Which system includes XII, XI, IX, VIII?
Intrinsic system
Which system is mostly VII?
Extrinsic system
Which pathway includes X, V, IV, III?
The common pathway
What is the purpose of Thrombin in the coagulation cascade?
Converts fibrinogen (Factor I) to Fibrin (Factor IA)
What is the purpose of Fibrin (Factor Ia) in the coagulation cascade?
Form a meshwork around the platelet plug
The extrinsic and intrinsic pathways of coagulation meet where?
The common pathway
What factors are in the common pathway?
Factors 10, 3, 4, 5, 2, 1
What does the common pathway produce?
Factor 10 and Factor 5 and phospholipid form the prothrombin complex to convert prothrombin (Factor II) to Thrombin (Factor IIa) which converts Fibrinogen (Factor I) to Fibrin (Factor Ia)
What is the only factor in the extrinsic pathway for coagulation?
Factor 7
What stimulates factor VII of the extrinsic pathway?
Release of Factor 3 (Tissue thromboplastin) from traumatized tissue (Re: 3+7 = 10, 10 is the common pathway)
What are the factors in the intrinsic pathway?
12, 11, 9, 8
What stimulates the intrinsic pathway and what is the factor that starts off the intrinsic pathway?
Collagen from vessel wall and injured tissue activates factor 12
Collagen from the vessel wall and injured tissue not only activates Factor 12 of the intrinsic pathway, they also activate what?
Platelets. The platelets fwill produce PF3 which will come back into play at the end of the intrinsic pathway as Factor 9a interacts with Factor 8 and PF3 to stimulate Factor 10 of the common pathway
Factor 12 activated, becomes Factor 12a, and requires what two things to activate Factor 11?
- Kininogen
2. Prekallikrein
Once Factor 11 is activated by Factor 12a + kinenogen + prekallikrein, and becomes factor 11A, it activates what Factor next in the intrinsic pathway?
Factor 9
Factor 9 becomes Factor 9a after activation by Factor 11a, and Factor 9a activates what next and in what pathway?
Activates Factor 10 of the common pathway
What must factor 9a have help in order to activate Factor 10 of the common pathway?
Factor 8 and PF3
When Factor 10 is activated by Factor 9a + Factor 8 + PF3, what is created?
Factor 10 + Factor 5 + phospholipids form Prothrombin activator to activate Prothrombin (Factor II) to Thrombin (Factor IIa) which will activate Fibrinogen (Factor I) to Fibrin (Factor Ia)
Why do we want to know if a patient has liver disease?
Every proenzyme (except for Factor 8) are made in the liver. If the function of the liver is not good, you won’t have good clotting.
Why does cancer affect clotting?
Radiation therapy affects bone marrow, where the clotting happens
What is required for the Prothrombin activator (Factor 10 + Factor 5 + phospholipids) to convert Prothrombin (Factor 2) to Thrombin (Factor 2a)?
Calcium
Where is prothrombin (Factor 2) synthesized and on what vitamin does it depend?
- Liver
2. Vitamin K
What substance is Thrombin (Factor 2a)?
Proteolytic enzyme that acts on fibrinogen (Factor 1)
Fibrin (Factor IA) is syntehsized where and is it a monomer or a dimer?
- Liver
2. Monomer that polymerizes with other fibrin monomers to form fibrin fibers
As a dentist, can you order a CBC?
Yes
Are the initial bonds between fibrin (Factor Ia) monomers strong or weak?
Weak
What strengthens the bonds between fibrin monomers as they polymerize to make fibrin?
Fibrin stabilizing factor
Where is fibrin stabilizing factor released from?
Plasma globulin
Platelets
What is required toa ctivate fibrin stabilizing factor?
Thrombin (Factor 2)
What does the clot contain once it is interwoven with the fibrin (Factor Ia) from the coagulation cascade?
Meshwork entraps blood cells, platelets, and plasma
What occurs in the clot once the coagulation cascade has worked?
Platelets activate contractile proteins: thrombosthenin, actin, myosin. Causes stronge shrinkage and clot contraction.
What is the purpose of the clot contraction?
The clot sealed the open vessel and the contraction brings the open edges together to increase hemostasis
What causes clot fibrinolysis during the fibrinolytic phase?
Plasmin (a plasma protein)
Plasmin is an activated form of what?
Plasminogen
Where is plasminogen (inactive form of plasmin) intitially?
Entrapped within the clot
How is plasminogen activated to Plasmin within the clot to begin fibrinolysis?
Converted via tissue plasminogen activator, t-PA
What releases t-PA to activate plasminogen in the clot to plasmin to cause fibrinolysis?
Released slowly from injured vessel and tissue so it accumulates over a few days then activates plasminogen to plasmin
What wil plasmin digest?
- Fibrin fibers
- Prothrombin (Factor 2)
- Factor 5
- Factor 8 (intrinsic)
- Factor 12 (intrinsic)
Where is the plasmin also found beyond the clot?
Saliva
Why is the plasmin in saliva a concern?
Patient with high salivary plasmin is at increased risk for alveolar osteitis (Dry socket) as the plasmin fibrinolysis the clot prematurely.
How soon after a vascular injury that causes exposed subendothelium does vascular constriction occur?
Constriction is immediate
How soon after a vascular injury that causes exposed subendothelium does platelet adhesion occur?
1-2 seconds
How soon after a vascular injury that causes exposed subendothelium does platelet aggregation occur?
10-20 seconds
How soon after a vascular injury that causes exposed subendothelium does the platelet plug form?
1-3 minutes
How soon after a vascular injury that causes exposed subendothelium does consolidation of the platelet plug occur?
3-5 minutes
How soon after a vascular injury that causes exposed subendothelium does fibrin stabilization of the plug occur?
5-10 min
How soon after a vascular injury that causes exposed subendothelium does the coagulation cascade take to complete?
Hours
How soon after a vascular injury that causes exposed subendothelium does clot breakdown occur?
Days
How much blood loss should you expect in a hemophiliac during extraction and why?
Normal during extraction and immediately post-op because their platelets are fine
When is the concern with clotting in a hemophiliac with respect to an extraction?
8 hours post op because their coagulation cascade is messed up
What is the concern with hemostasis and cancer treatment, radiation therapy, and chemotherapy?
They affect the bone marrow where platelets are made
What is the most common site for spontaneous bleeding?
Nose
What is the normal range for platelet count?
145k to 350k
What are 4 laboratory tests for hemostasis?
1, Platelet count
- Bleeding time (BT)
- Partial Thromboplastin Time (PTT)
- Prothrombin Time (PT)
What is a lab test that reflects the patient’s ability to form and develop mature platelets. It is only a numerical count, and does not indicate the quality of the platelets
Platelet count
What is an abnormal platelet count?
Below 100,000
What platelet count requires platelets administered to the patient before an extraction?
Less than 50,000
What platelet count has a risk for spontaneous intracranial hemorrhage (ICH)
Less than 20,000
What lab test determines the quality of platelet function, i.e. platelets ability to form a plug after activation, done with a BP cuff at 40mmHg 6mm by 1mm incision on the forearm and blood absorbed by filter paper at 30 sec intervals until bleeding stops?
Bleeding time test
What is the upper limit of normal bleeding time?
7.5 minutes
Partial thromboplastin time (PTT) measure what 2 parts of the coagulation cascade?
Intrinsic and common
Prothrombin time (PT) measures what part of the coagulation cascade?
Extrinsic and common
Why does the partial thromboplastin time (PTT) only measure the intrinsic and common pathway?
Because factor 7 (extrinsic) and Factor 13 are not detected
What is mixed with the plasma sample to get the PTT to measure the prothrombin time?
Phospholipid (phospholipid binds with Fact 10 and Factor 5 in the common pathway to get prothormbin activator complexa nd eventually fibrin. Intrinsic pathway must work (12 to 11 to 9 and 8 and PF3) to get a clot. The speed at which this occurs measures the ability of the intrinsic and the common pathways
What is the normal range for a PTT (measure of the intrinsic and common pathways)?
28-34 seconds
What patients would show a prolonged PTT?
- Von Willebrand’s disease (factor 8 intrinsic)
- DIC (Diffuse Intravascular Coagulation)
- Fibrinogen dysfunction (common pathway)
- Heparin Use (anticoagulant)
Prothrombin time (PT) screens for abnormalities in what factors?
7 (extrinsic)
10 (common)
5 (common)
2 (common = Thrombin)
What patients would a PT be used to screen?
- Warfarin patients
- Liver damage (where 7 and thrombin are made)
- Vitamin K deficiency (Vitamin K is required for Factor 2 Thrombin)
What is a normal range for PT?
10-12 seconds
Why use PTT to measure a Heparin patient and PT to measure a Warfarin patient when both patients are taking an anticoagulant?
Heparin inactivates thrombin (Factor II common path) and also Factors 9 (intrinsic), 10 (common), 11 (intrinsic), and 12 (intrinsic) and prevents conversion of fibrinogen to fibrin (common). Only acting on the common pathway, so must test with PTT. Warfarin/Coumadin depletes Vitamin K which reduces synthesis of clotting factors in the liver that require Vitamin K (2 (common) 7(extrinsic), 9(intrinsic), and 10 (common)). Therefore, the extrinsic and common path is indicated as 7 is affected and the only test that reads Factor 7 is PT.
What is the international normalized ratio (INR)?
INR = (patient’s protime / mean of normal range)
What surgical therapy can be done on a patient with INR less than 3.5?
Single extraction with local measure (pack with gel foam, suture, maybe topical thrombin)
If the patient has thrombocytopenia, marrow disease, or on a chemotherapeutic drug, what lab test should be ordered before performing surgery?
Platelet count (norm 145k to 350k)
If a patient is taking aspirin (ASA, COX-1 inhibitors (aspirin does this) or other drugs that inhibit platelet aggregation, what lab test should be ordered before performing surgery?
Bleeding time (high end is 7.5 min)
If a patient is taking Coumadin or Warfarin, has liver disease (think Vitamin K problem and factor synthesis problem) or has a vitamin malabsorption problem, what lab test should be ordered before performing surgery?
PT/INR (PT norm is 10-12 seconds, desired INR is ????????)
If a patient was given Heparin IV in the hospital or takes Pradaxa, or has Von Willebrand’s disease, what lab test should be ordered before performign surgery?
PTT (norm 28-34 seconds)
What are 3 classifications of bleeding disorders?
- Disorders of coagulation
- Non-thrombocytopenic purpura
- Thrombocytopenic purpura
What are 2 inherited disorders of coagulation?
- Hemophilia A (X-linked (males), Factor 8 deficiency)
- Hemophilia B (Christmas disease, Factor 9 deficiency)
NOTE: Both are intrinsic pathway problems, test with PTT
What are 6 examples of acquired disorders of coagulation?
- Liver disease
- Vitamin K deficiency
- Anticoagulant therapy
- DIC
- Primary fibrogenolysis
- Marrow disease
How much of liver must be gone before the patient has bleeding problems?
70%
What are the Vitamin K dependent clotting factors?
Factor 2 (common) Factor 7 (extrinsic) Factor 9 (extrinsic) Factor 10 (common)
What is a DIC (disseminated intravascular coagulopathy)?
All clotting factors get used up and patient bleeds out. This is a risk following labor.
When is the danger with coagulation for a Hemophilia patient?
Hours after an extraction. They formed a platelet plug but lack factor 8 (Hemophilia A) or factor 9 (Hemophilia B) meaning the platelet plug will not be stabilized by fibrin and the patient will start to bleed again
Which hemophilia is more common?
Hemophilia A (factor 8 deficiency) 1:5k to 10k Hemophilia B (factor 9 deficiency) 1:2.5k to 30K
Non-thrombocytopenic purpura bleeding disorders have to do with what?
Abnormal vascular wall integrity which prevents normal contraction at injury or a platelet aggregation problem
What are examples of things that can lead to non-thrombocytopenic purpuras?
- Connective tissue vascular disease (Systemic Lupus Erythemous, Scleroderma)
- Vitamin C deficiency (Scurvy)
What is the most common non-thrombocytopenic purpura that are caused by platelet function problems?
Von Willebrand’s Disease
What ist he most common inherited bleeding disorder?
Von Willebrand Disase
What is Von Willebrand factor?
A bridge that binds platelets and endothelial cells
A carrier protein for Factor 8 (intrinsic path)
A person with Von Willebrand’s disease will have what type of PTT?
Abnormal PTT (due to factor 8 problem) increased bleeding time (because platelet aggregation is messed up)
How can von Willebrand disease be treated?
- Factor 8 replacement
- Desmopressin (increases VWF, Factor 8 and t-PA, shortening PTT and bleeding time)
- Antifibrinolytics
- Topical thrombin
All of the clotting factors are made in the liver except for what?
Factor 8
What is Dr Strauss’s rule for herbal supplements?
Anything starting with a G causes bleeding: Gingko bilboa, Garlic, Saw Palmetto (?)
For a patient with a marrow disease resulting in thrombcytopenia, what is the desired platelet count for low bleeding risk procedure?
50-70K platelets
For a patient with a marrow disease resulting in thrombocytopenia, what is the desired platelet count for high bleeding risk procedure?
80K platelets
An apheresis unit (6 pack) is expected to raise the platelet by how much in how long?
30K platelets w/in 10 minutes to 1 hour
Anything that poisons a platelet lasts for how long?
Platelet lifetime = 7 days
Heparin is used on what patient type and how will this affect treatment scheduling?
Patient on renal dialysis. Perform procedures on non-dialysis days
What is a concern if patient is on long-term antibiotic therapy?
Vitamin deficiency leading to a non-thrombocytopenic purpura caused by lack of Vitamin K uptake in gut
Which is shorter-acting: coumadin or heparin?
Heparin
How long after stopping coumadin should it take to get a normal PT?
2-3 days
Is stopping anti-platelet therapy (Aspirin or Plavix) necessary prior to surgical procedure and what must the patient be told?
No. Inform the patient that they will bleed longer.
A patient that has one of the following: prosthetic valve, atrial fibrillation, DVT, stroke risk, or hypercoagulable state would be given what drug and what test would we use to determin their coagulation ability?
Coumadin
PT
What patient types are at a high risk when taken off of Coumadin?
Mitral Valve patient A-Fib patient more than 75 years old Diabetics DVT early in the diagnosis (less than 2 months) Hypercoagulable
If a patient is on Pradaxa and has more than 50ml/min of creatine clearance, how long must they be off the Pradaxa before dental treatment?
1-2 Days, then restart once hemostasis is achieved
What is Lovenox?
Low molecular weight Heparin used to bridge patient perioperatively from other anticoagulants. Stopped 24 hours prior to procedure to allow 5 half-life eliminations (half-life is 4-6 hours)
When patient is bleeding, what is most important?
Find out why bleeding (local or systemic)
What is a characteristic of oral bleeding with a systemic cause?
Will be generalized and out of magnitude to injury
If bleeding is immediate what is the cause?
Physical
Early bleeding after treatment is what cause?
Platelet problem
Loss of clot
Delayed bleeding after treatment is what cause?
Coagulation problem
Loss of clot
What is an immediate treatment for bleeding?
Pressure
What are other methods to stop bleeding beyond pressure?
- Gel foam scaffold
- Topical thrombin to catalyze fibrin
- Amicar to inhibit plasmin and maintain clot
- Cautery/siler nitrate to coagulate cellular proteins
- DDAVP (Desmopressin) to increase VWF and contraction of vasculature
- Blood products
What is a homeopathic method for pressure to stop bleeding?
Bite on teabag, which release tannic acid
What is the problem with giving epinephrine for hemostasis?
False sense of hemostasis
What is indicated for injection hematoma from doing PSA?
Long-term pressure, antibiotics, follow for infection or trismus
Hypercoagulability is most commonly caused by what?
Factor 5 Leiden mutation
A patient taking Aspirin for heart disease prevention that has early bleeding with EXT, bleeding is caused by what?
Imparied platelet aggregation
