Clotting and Bleeding Flashcards
Primary Hemostasis
- arterial vasoconstriction, to reduce blood flow to the injury site. 2. VWF released, the wall becomes “sticky” 3. Platelet adhesion- initial platelet is friable and can be washed away one vasorelaxation occurs.
Secondary Hemostasis
involves and intrinsic and extrinsic pathway
Intrinsic pathway
this is contact activation. when blood hits exposed collagen, it activates factor XII
Extrinsic Pathway
the damaged tissue itself releases tissue factors, which complex with factor VII
The work horse of the coag cascade
Thrombin Activates 5, 7, 8, 11, 13
Vitamin K dependent clotting factors
II VII IX X
Factor I
Fibrinogen
Factor II
Prothrombin
Factor III
Tissue factor, or thromboplastin
Factor VIII
Anti-hemophillic factor
Factor IX
Christmas factor
Bleeding disorders and genetics
30-40% of patients with Hemophilia A or B do not have a family history!
Signs indicating it is a platelet defect
Mucocutaneous bleeding of oral cavity, nasal, GI, GU Increased bleeding after cuts Small areas of superficial bleeding Variable amounts of bleeding after major surgery immediate
Signs indicating it is a clotting defect
Deep tissue bleeding (joint and muscle) Large hematomas Can be delayed bleeding post-surgery
Platelet disorders
Von Willebrand disease (most common) Immune thrombocytopenia
Clotting deficiencies
Factor VIII (Hemophilia A) Factor IX (Hemophilia B) Factor XI (Hemophilia C)
Inherited coagulation disorders
Increased propensity for forming blood clots. Not all patients with a venous or arterial blood clot will have a coagulation disorder, but can be a factor in 50% of patients presenting before age 40. Risk for clots can also be increased in pregnancy, cancer and estrogen therapy.
Antithrombin
alpha-2 globulin made in the liver functions as a negative feedback moderator- is an anticoagulant. Works on Thrombin and factor Xa. Deficiency increases coagulation (if this goes unchecked, can deplete all clotting factors and eventually will result in uncontrollable bleeding).
decreased antithrombin manifestations
DVT Pulmonary embolism Phlebitis Heparin resistance getting clots early in age

Protein C
Anticoagulant, synthesized in the liver
•inhibits factor Va and factor VIIIa
Vitamin K dependent
Test with Protein S
Protein S
anticoagulant, made in the liver
•co-factor to protein C and enhances the function of Protein C
vitamin K dependent
Protein C/S defeciency manifestation
- Venous thromboembolism (VTE) → increased risk 7 fold!
- Disseminated Intravascular Coagulation
- Neonatal purpura fulminans

Factor V Leiden
inherited, mutated form of factor V
Doesnt allow protein C to cleave at normal site, so it stays in circulation longer, increasing coagulation
Test indicated in pts who have had a thrombotic event without any other predisposing factors, if pt has a strong family hx of thrombosis, DVT when pregnant or on OCP
Fibrinogen
clotting factor, produced in the liver
is converted to fibrin via Thrombin
Is an acute phase reactant
Dysfibrinogenemia
§Dysfunctional fibrinogen, bleeding or thrombosis occurs, poor wound healing
§Hypofibrinogenemia
Reduced fibrinogen, usually mild bleeding
§Hypodysfibrinogenemia
Reduced AND dysfunctional fibrinogen, bleeding or thrombosis
§Afibrinogenemia
§Rare genetic condition resulting in complete lack of fibrinogen (↑ in consanguinity)
results in mild-severe bleeding
Bleeding time
test that can be useful in evaluating platelet function, but is not super reproducible
An incision 1mm deep x 10 mm long is made into the skin, and a stopwatch records the time. Every 30 seconds, a filter paper is applied over wound. Once the filter paper no longer absorbs blood, the test time is recorded.

Normal bleeding time
1-9 minutes
Abnormal bleeding time
9-15 minutes indicative of platelet dysfunction
>15 minutes is critical
Increased bleeding time
due to : decreased platelet count
fibrinogen defeciency
VW disease
medications (NSAIDs)
Liver failure
Leukemias
Prothrombin time/
International Normalized Ratio (PT/INR)
- “ProTime” or “INR”
- Useful in the evaluation of the factors I (fibrinogen), II (prothrombin), V, VII, and X ( i.e., the extrinsic system and common pathway).
- Tissue factor is added to the blood sample and the time that it takes to clot is measured.
•If these clotting factors are deficient, the Prothrombin Time is prolonged…takes more time to clot
•Primarily used to monitor patients on warfarin therapy
MEASURES THE EXTRINSIC PATHWAY

PT/INR normal
PT: 11.0-12.5 seconds
INR: 0.8-1.1
Critical when INR > 5
Ideal INR for DVT/treatment
2-3
Partial Thromboplastin Time
commonly used to evaluate the patient who is on heparin therapy for anticoagulation (heparin inactivates Factor II
•The PTT evaluates factors I, II, V, VIII, IX, X, XI, and XII –> the intrinsic pathway
Activated PTT
aPTT- activator is added to a PTT test. Basically decreases clotting time in half
PTT/aPTT normal
aPTT: 30-40 seconds
PTT: 60-70 seconds
Thrombin time
assesses the amount of fibrin formation that is occurring
Normal less than 20 seconds, but this depends on the lab
thrombin time is increased in congenital or impaired hypofibrinogemia and DIC
prefferred INR for orthopedic surgery
preferred INR for A fib
2-3
preferred INR for prosthetic valve prophylaxis
2.5-3.5
Prostate Specific Antigen
a glycoprotein expressed in normal and neoplastic prostate tissue, but usually expressed in higher concentration in prostate cancer cells.
Not specific though, as more frequently elevated in hyperplasia and inflammation of the prostate
PSA normal
•0.00-4.00 ng/ml
% of men with prostate ca who have a normal PSA
PSA velocity
Some clinicians use this instead of PSA alone
PSA velocity > 0.75 ng/mL/year can be correlated with prostate cancer. Serial, annual measurement used x 3 years.
free PSA
Another measurement for prostate ca, possibly more accurate than PSA.
•ratio of free-to-total PSA is reduced in men with prostate cancer.
CA125
•most often present in ovarian carcinoma- but levels can vary in different cell types
•Due to immensely low specificity and sensitivity, this test is not recommended as a screening tool currently
women with ovarian cancer will have their CA125 levels measured to evaluate therapy.
CA125 can also be elevated in breast, colon, liver, pancreatic and lung cancer. Can also be high in systemic illnesses like infection and autoimmune.
OVA-1
test that uses 5 biomarkers to evaluate if an adnexal mass is cancerous before surgery, identify if a pt with an ovarian mass is high risk, and identify cancers that were previously missed with CA125

Beta-2 macroglobulin
1 of the 5 biomarkers in OVA-1
is
CA 125II
1 of the 5 biomarkers of OVA-1
2nd generation CA125
Apolipoprotein A1
1 of the 5 biomarkers in OVA-1
◦involved in cholesterol transport but has some role in tumor suppression
decreased in ovarian CA
Prealbumin
1 of the 5 biomarkers in OVA-1
◦decreases with tumor burden due to metabolic changes that occur in cancer
Transferrin
1 of the 5 biomarkers in OVA-1
down-regulated in ovarian cancer
Carcinoembryonic antigen
CEA
•CEA is a protein normally found in fetal tissue, levels usually disappear after birth, but may be present in colon
- CEA is used to monitor response to chemotherapy or post-surgery in colon cancer
- Serial measurements recommended to detect recurrence of tumors
- CEA not recommended as a screening test as sensitivity can vary from 4% (breast cancer) to 70+% (colon and rectal cancer)
CEA can also be elevated in benign states- GI infection/inflammation and smoking.
•
Cancer Antigen 19-9
CA19-9 is present in epithelial tissues of many organs
•most frequently used to monitor disease response to treatment with pancreatic cancer.
- not recommended as a screening test for pancreatic or colon cancer
- Preoperative levels correlate with outcome
- Rising levels correspond with recurrence and shorter survival time.
Cancer Antigen 15-3
- Most often used in breast cancer patients and most widely used serum marker in diagnosis of breast cancer
- Levels correspond with progression or regression of disease
- Higher levels correspond with greater tumor size or disease burden/stage and highest levels tend to occur with metastasis to bone or liver
Does have low specificity and sensitivity
CA 27-29
variation of CA 15-3
can also be used in Breast cancer marking
Alpha-fetoprotein
•AFP is produced in fetal liver, yolk sac, and GI tract, therefore infants can have very high levels
- In adults, AFP is most commonly used marker for hepatocellular cancer
- AFP levels do not correlate well with size of tumor, stage of cancer or prognosis of disease.
- Values over 500 mcg/L in a patient at high-risk for hepatocellular carcinoma is nearly diagnostic of the disease (normal value in non-pregnant patient < 40mcg/L)
- High false negative rate- serum levels are normal in 40% HCC patients
Serum calcitonin
used in detection of Medullary Thyroid Carcinoma (MTC)- production of calcitonin is characteristic of MTC.
•elevated calcitonin level correlates with tumor size pre-operatively
Calcitonin can also be elevated in other cancers that have bony mets, and in non ca diseases of the thyroid