Hematology II Flashcards
The Right Lymphatic Duct and the Thoracic Duct drain into what veins?
Subclavians
An increase in ____ or a decrease in ____ will lead to edema.
Pc
Pi-c
When is the Thymus largest?
What does it produce?
Located?
Puberty
WBC - especially T-lymphocytes
Mediastinum
Three sets of Tonsils:
Pharyngeal (adenoids)
Palatine
Lingual
Where is the Mucosa Associated Lymphoid Tissue (MALT)?
Mucosal epithelium of the intestine
*B and T lymphocytes
A defect in what will cause bleeding or thrombosis?
Hemostasis
From whence do platelets come?
Megakaryocytes
How many platelets can a single megakaryocyte produce?
3000
What percentage of platelets are pooled in the spleen?
What is the normal level of platelets in the blood?
20-30%
250k - 400k / mm3
T/F
Platelets contain granules
True
What is the average lifespan of a platelet?
5-20 days
What layer is different in veins?
Thinner tunica media
What is the anatomy of a capillary?
Tunica Intima only
(no media or external)
Contains endothelial cells and small amount of collagen
The body’s first reaction to injury is the ____ phase.
Vasoconstrictive
aka Vascular Spasm
What is the vasoconstrictive phase triggered by?
Sympathetic system
direct injury itself
What is the precursor to a blood clot?
Platelet plug
What receptors on platelets bind collagen structure and form a plug?
GP1a
Where is von Willebrand’s Factor found?
plasma
platelets
bv walls
What binds to von Willebbrand’s Factor?
GP1b receptors
*on platelets
First 2 steps of platelet plug formation:
GP1a attaches to exposed collagen
Gp1b attaches to von Willebrand’s Factor
What are the 3 platelet granules released upon adhesion?
ADP
Thromboxane A2 (prostaglandin)
Serotonin (5-HT)
What do ADP, TXA2, and 5-HT do once released from platelets?
Bind/recruit other platelets
Aggregate
What platelet receptor is responsible for aggregation of the platelet plug?
What does it bind?
GPIIb
Fibrinogen
Where are most clotting factors synthesized?
Liver
Blood clotting factors I, II, III
Fibrinogen
Prothrombin
Tissue factor/thromboplastin
Blood clotting factors IV, V, VII
Calcium
Proaccelerin (labile)
Proconvertin (stabile)
Blood clotting factors VIII, IX, X
Antihemophilic factor A/globulin
Antihemophilic factor B, Plasma thromboplastin component, Christmas factor
Stuart-Prower factor
Blood clotting factors XI, XII, XIII
Plasma thromboplastin antecedent, Hemophilia C, Rosenthal syndrome
Hageman factor
Fibrin stabilizing factor, Laki Lorand factor
What blood clotting factors are not made in the liver?
4 factors
III - perivascular tissue
IV - Plasma
XII - Platelets (and liver)
XIII - Platelets, plasma
What blood clotting factors are Vitamin K dependent?
4 factors
II - Prothrombin
VII - Proconvertin (stable)
IX - Ab, PTC, Xmas
X - Stuart-Prower
Extrinsic clotting cascade:
III - thromboplastin
IV - Ca
VII - Proconvertin
V - Proaccelerin
X - Stuart Prower
Intrinsic clotting cascade:
XII - Hageman
XI - Plasma thromboplastin antecedent
(aka Rosenthal, Hemophilia C)
IX - Plasma thromboplastin component
(aka Christmas, Anti-hemophilic factor B)
VIII - Anti-hemophilic factor A / Globulin
X - Stuart Prower
Common clotting cascade:
X - Stuart Prower
III (thromboplastin), V (proaccelirin), IV (Ca), PF3
Prothrombin Activator
II - Prothrombin > Thrombin (feedback V - proaccelirin)
I - Fibrinogen > Fibrin >
XIII - Laki Lorand (Fibrin stabilizing), Ca >
Fibrin Polymer
Name 3 Anti-coagulants that help to balance Hemostasis:
Thrombomodulin
Antithrombin III
Heparin cofactor II
How does Thrombomodulin work to shut down the coagulation pathway?
Thrombomodulin-Thrombin Complex forms activated Protein C and Protein S deactivates V and VIII
Which anti-coagulant is a glycoprotein produced by the liver that binds Factor X?
Antithrombin III
What does Heparin cofactor II inhibit?
What type of protein is it and where is it synthesized?
Thrombin
Plasma
Liver
What enzyme initiates the breakdown of a blood clot?
Plasmin
from Plasminogen
What converts Plasminogen to active Plasmin?
and thus initiated Fibrinolysis
Tissue Plasminogen Activator (t-PA)
What releases t-PA into the blood?
Damaged endothelium of vessels
Where is the Plasminogen that degrades a clot found?
In the clot
T/F
Plasminogen is fast acting
False
very slow to break down fibrin mesh
What are 2 tPA inhibitors?
Plasminogen activator inhibitor 1
Plasminogen activator inhibitor 2
What are 2 Plasmin inhibitors?
Alpha2-antiplasmin
Alpha2-macroglobulin
What is a low platelet count?
from blood smear
Thrombocytopenia
What can thrombocytopenia lead to?
4 things
Purpuria (purple spots)
Petechia (pinpoint hemorrhages)
nosebleeds
gum bleeds
Some inherited platelet disorders are associated with…
large platelets
What is the function of Sodium Citrate in coagulation tests?
Removes Calcium
What is the coagulation test for the Extrinsic Pathway?
After Calcium, what is added?
How long before clotting occurs if normal?
Prothrombin Time (PT)
Brain Thromboplastin
12-15 seconds
What standardizes differences in various companies coagulant factors used for testing?
What is the particular constant for a coagulant called?
International Normalized Ratio (INR)
ISI - international sensitivity index
When is the INR normally used?
Warfarin (coumadin) usage
What is the normal INR for someone using Warfarin?
- 0 - 3.0
* 2.5 - 3.5 if high risk for clot formation
What tests the Intrinsic Pathway?
Activated Partial Thromboplastin Time (APTT)
In the APTT test, what is activated after Calcium?
Kaolin
Phospholipids
How long does clotting normally take in the APTT coagulation test?
25-36 seconds
What is the APTT test most often used to monitor?
Heparin
What tests the Common Pathway for coagulation time?
Thrombin Clotting Time (TT)
After Calcium what is added to the Thrombin Clotting Time test?
(common pathway test)
Thrombin
*assesses Fibrinogen > Fibrin conversion
When is the TT (Thrombin Clotting Time) test used?
If Prothrombin (extrinsic) or APTT (intrinsic) tests are prolonged
What determines actual deficiencies for specific clotting disorders?
Coagulation Factor Assays
If there is a prolongation of APTT test and PT is normal, what x-linked disorder might the patient have?
Hemophilia A or Hemophilia B
What is the prevalence of Hemophilia A?
1 in 5000 males
T/F
Hemophilia A is strictly genetically inherited
False
30% new mutations on VIII
What is mutated in Hemophilia A?
VIII (antihemophilia factor A/globullin)
What is mutated in Hemophilia B?
Another name?
prevalence?
IX
Christmas disease
1 in 30,000
What are the 4 areas of most concern in hemophiliacs?
Joint capsules
Skeletal muscles
GI tract
Brain
What process in joints caused hemophiliacs pain?
Healing
*breaks down bone
What tests will be prolonged in Von Willebrand’s Disease?
APTT and PT
Why will PT be prolonged in Von Willebrand’s disease if Factor VIII is the primary pathological concern?
Platelet adhesion is also disrupted
What is the most common inherited bleeding disorder?
Von Willebrand’s Disease
125 per million
T/F
Von Willebrand’s Disease is mild and occurs mainly in the skin
True
What 2 pathologies are seen in Von Willebrand’s disease?
Platelet adhesion disrupted
Factor VIII
What can disrupt production of platelets and cause Thrombocytopenia?
Drugs
marrow failure
What can destroy platelets and cause Thrombocytopenia?
Idopathic thrombocytopenic purpura
*autoimmune
What removes platelets in ITP - Idopathic thrombocytopenic purpura?
Reticuloendothelial system
What conditions are associated with excessive clotting?
Thrombophilias
What are 4 examples of Inherited Thrombophilias?
Protein C deficiency
Protein S deficiency
Activated Protein C Resistance
Antithrombin III deficiency
What causes Activated Protein C resistance?
Factor V responds poorly to Protein C
*mutation in factor V Leiden gene
What % of North American caucasians have a Factor V Leiden Mutation?
3-8%
List the 4 inherited Thrombophilias in terms of prevalence?
Factor V Leiden
Protein C deficiency
Antithrombin deficiency
Protein S deficiency
What are the 4 main categories of drugs affecting hemostasis?
Anticoagulants
Thrombolytics (destroy clots)
Antiplatelets
Antifibrinolytics (promote clots)
What are the 4 main divisions of anticoagulant drugs?
Indirect thrombin inhibitors (Heparin)
Coumarin (Warfarin)
Direct Thrombin inhibitors
Direct Factor X inhibitors
What are the 2 most common Heparins?
mixtures of proteins
Unfractionated heparin (UFH) - Heparin Sodium
Low molecular weight heparin (LMWH) - Fragmin, Innohep, Lovenox
How is Heparin an indirect thrombin inhibitor?
Increases Antithrombin III’s activity, which shuts down factor X (Stuart-Power)
Stimulates Heparin cofactor II (also inhibits thrombin)
T/F
UFH - unfractionated heparin can be given orally
False
Proteins are destroyed in stomach
Why is UFH a variable anticoagulant?
Binds many proteins in body
*individually variable
What test is used to monitor UFH?
What is normal?
By how much will theraputic levels of UFH prolong?
APTT
25-36 seconds
2-2.5 times normal values
How are Low Molecular Weight Heparins administered?
What determines dose?
Does it need to be monitored?
Subcutaneously
Body weight
No
How does Warfarin work?
Interferes with Vitamin K synthesis
What factors are dependent on Vitamin K?
and therefore stopped by Warfarin
II
VII
IX
X
T/F
Warfarin is used in prophylaxis of venous thrombosis, Pulmonary embolism, artificial heart valves, atrial fibrillation, surgery
True
The INR - international normalized ratio for Warfarin is…
2.0 - 3.0
What drugs inhibit Warfarin metabolism?
thus accumulating warfarin and increase effects
Cimetidine, acetaminophen, acute alcohol, antibiotics (azithromycin, cipro, clarithromycin, erythromycin)
What hormone can increase catabolic breakdown of clotting factors and enhance the effects of Warfarin?
Thyroid hormones
What drugs diminish effects of Warfarin?
Chronic alcohol
Phenytoin
Oral contraceptives
What food decreases the effects of Warfarin?
Vitamin K
T/F
Warfarin is fine during pregnancy, Heparin is not.
False
Warfarin is teratogenic - causes birth defects
Heparin is fine
How are Direct Thrombin Inhibitors Administered?
What is the main DTI?
Orally
Dabigatran
What are the advantages of Direct Thrombin Inhibitors?
non-reactive with blood proteins
Orally taken
No constant monitoring
What are some Direct Factor X inhibitors?
Rivaroxaban
Apixaban
Endoxaban
What type of drug is used in emergencies for Ischemic Strokes?
Thrombolytics
How do Thrombolytics work?
tPA - tissue plasminogen activator Forms Plamin (from Plasminogen) to break down clot
Name 3 Thrombolytics:
Streptokinase
Urokinase
Synthetic tPA
Name the 3 classes of Antiplatelets.
Cyclooxygenase Inhibitors (aspirin)
Thienopyridines (ADP inhibitors)
GP IIb/IIIa inhibitors
How does Aspirin act as an anticoagulant?
Inhibits synthesis of TXA2
aggregating factor
How do Thienopyridines (ADP inhibitors) work?
Prevent ADP - Platelet binding
prevents aggregation
What is an ADP inhibitory drug?
(Thienopyridine)?
Clopidogrel
What class of drugs inhibit the “final common pathway” for platelet aggregation?
Example of drug:
How administered?
Glycoprotein IIb/IIIa inhibitors
abciximab
I.V.
What is an antifibrinolytic drug?
Tranexamic acid
How is Tranexamic Acid used in dentistry?
5% mouth rinse in pts with prolonged bleeding times
How does tranexamic acid work?
Prevents the formation of Plasmin by Plasminogen
(plasminogen inhibitor) by tPA
What is the risk of developing thromboembolism if you stop taking Warfarin for 2 days?
0.02 to 1%
T/F
It is safer to continue taking Warfarin throughout dental procedures and recovery.
False.
Safer to stop taking
What is the recommended INR before dental surgery for patients on Warfarin?
Less than 4
What solution is easier to make and less expensive than tranexemic acid?
Aminocaproic Acid
T/F
Aminocaproic Acid isn’t available in Canada.
True
