Lecture 14: Blood Flashcards
What initiates primary hemostasis in the coagulation cascade?
arterial vasoconstriction occurs to reduce blood flow to the site of the injury
What is involved in secondary hemostasis?
the two pathways: intrinsic and extrinsic
What is the intrinsic pathway in the coagulation cascade?
contact activation: the blood is exposed to the surface of the damaged endothelium and collagen within that wall and this contact activated factor XII to XIIa
What is the extrinsic pathway in the coagulation cascade?
traumatized tissue releases tissue factors which complex with factor VIIa
factory I
fibrinogen
factor II
prothrombin
factor III
tissue factor or thromboplastin
factor VIII
antihemophilic factor
factor IX
Christmas factor
What are the vitamin K dependent clotting factors?
II, VII, IX, and X
What is an good indication of the presence of an inherited bleeding disorder?
bleeding after minor surgical procedures especially dental procedures
What is the percent of patients with hemophilia A or B that have a negative family history?
30-40%
What are the indications of a platelet defect?
mucocutaneous bleeding after cuts, increased bleeding after cuts, small areas of superficial bleeding after cuts, variable amounts of bleeding after major surgery
What are the indications of clotting factor deficiencies?
deep tissue bleeding (joint and muscle), large hematomas, can be delayed bleeding post-surgery
What are examples of platelet disorders?
Von Willebrand disease is most common, immune thrombocytopenia
What are examples of clotting deficiencies?
factor VIII (hemophilia A), factor IX (hemophilia B), factor XI (hemophilia C)
What is a hyppercoagulable disorder?
usually results in higher than normal risk for thrombosis formation; also knows as thrombophilia or bleeding diathesis; increased risk involved in pregnancy, cancer, and estrogen therapy
What is antithrombin III?
also known as antithrombin; is an alpha-2 globulin made in the liver; it is an anticoagulant
What happens in the absence of antithrombin III?
coagulation is constant, unchecked and eventually results in depletion of clotting factors -> leading to uncontrolled bleeding
How is antithrombin involved in mediating the balance of clotting and bleeding?
inactivation of thrombin, and inactivation of factor X to Xa
What is an antithrombin III lab test used for?
used to monitor for hyppercoagulable states
What can a decreased antithrombin result in?
deep vein thrombosis, pulmonary embolism, phlebitis, heparin resistance, early age onset of thromboembolic events
What are protein C and protein S?
they are anticoagulants that are synthesized in the liver; protein s is a co-factor to protein c that enhances the function of protein C
What does protein C inhibit?
factor Va and factor VIIIa
What are the outcomes of a decrease in protein C and S?
increased risk 7 fold for venous thromboembolism (VTE), disseminated intravascular coagulation, neonatal purpura fulminans
What is factor V Leiden?
an inherited mutated form of factor V; caused by a single mutation from glutamine to arginine
What is the pathophysiology behind the effect of factor V Leiden?
typically protein C breaks down factor V at one of three cleavage sites; in factor V Leiden protein C cannon break down factor V at one of the normal cleavage sites -> as a result factor V leiden stays in circulation longer increasing coagulation
Who should you test for factor V leiden?
patients who have a thrombotic event without and predisposing factors; strong family history of thrombosis; DVT of pregnancy or w/ oral contraceptive use; arterial clot or thrombosis of unusual location
What is fibrinogen?
produced in liver; involved in hemostasis of blood clotting; fibrinogen is converted to fibrin through the action of thrombin; also is an acute phase reactant and levels increase with tissue inflammation
What is a fibrinogen test primarily used for?
used in the evaluation of bleeding disorders and to monitor for the treatment of DIC and fibrinolysis
dysfibrinogenemia
dysfunctional fibrinogen; bleeding or thrombosis occurs, poor wound healing
hypofibrinogenemia
reduces fibrinogen, usually mild bleeding
hypodysfibrinogenemia
reduced AND dysfunctional fibrinogen, bleeding or thrombosis
Afibrinogenemia
rare genetic condition resulting in lack of fibrinogen (increase in consanguinity); mild to severe bleeding
What causes increase in levels of fibrinogen?
acute inflammation, trauma, acute infection, CVA, CAD, MI, pregnancy, estrogen and oral contraceptive use
What causes a decrease in levels of fibrinogen?
congenital Afibrinogenemia, hypofibrinogenemia, liver disease, disseminated intravascular coagulation
What is normal bleeding time?
1-9 minutes
What length of bleeding time indicates a platelet dysfunction?
9-15 minutes
How is a bleeding time test performed?
an incision 1mm deep and 10mm long is made in the skin; every 30 seconds filter paper is applied over the wound; once the filter paper stops absorbing blood the time is recorded
What can increase and prolong bleeding time?
decreased platelet count, severe fibrinogen deficiency, von willebrand disease, medications such as NSAIDs and antibiotics, some connective tissue disease, liver failure, leukemia’s
What is prothrombin time/ international normalized ratio useful in the evaluation of?
factors I (fibrinogen), factor II (prothrombin), factor V, factor VII, and factor X; primarily measures the extrinsic pathway
How is a PT/INR test performed?
tissue factor is added to blood sample and the time that is takes to clot is measured; PT result is reported along with the INR result ( helps to standardize things across all labs)
What is the INR equation?
patients PT in seconds/ mean normal PT in seconds raised to the ISI……. ISI is the international sensitivity index
What is a normal value for PT/INR?
11.0-12.5 seconds (85%-100%)
INR: 0.8-1.1
What is a critical INR value?
greater than 5
In a patient with deep vein thrombosis prophylaxis or treatment what is the preferred INR?
2.0-3.0
In a patient undergoing orthopedic surgery what is the preferred INR?
2.0-3.0
In a patient with atrial fibrillation what is the preferred INR?
2.0-3.0
In a patient with prosthetic valve prophylaxis what is the preferred INR?
2.5-3.5
What can increase PT/INR values?
alcohol intake, diarrhea or malabsorption (vitamin K), liver disease, genetic factor definciency, vitamin K deficiency, ingestion of warfarin, DIC
What can decrease PT/INR values?
inadequate dosage of warfarin in patient on anticoagulation therapy
What is partial thromboplastin time (PTT)?
tis test is used to evaluate the patient who is on heparin therapy for anticoagulation; heparin inactivates fact II (prothrombin) and prevents formation of factor III (TF or thromboplastin), and is commonly used to prevent and treat blood clots
What factors does PTT evaluate?
factor I, II, V, VIII, IX, X, XI, and XIII; measures the intrinsic pathway
What is normal time for PTT?
60-70 seconds
What is normal time for aPTT?
30-40 seconds
How should a PTT or aPTT be modified for those receiving anticoagulant therapy?
1.5-2.5 times control value in seconds
What can increase PTT?
hemophilia and other clotting factor deficiencies, cirrhosis of the liver, vitamin K deficiency, DIC, warfarin administration
What can decrease PTT?
early DIC, extensive cancer
What is thrombin time?
assesses the amount of fibrin formation that is occurring
What is the normal range for thrombin time?
less than 20 seconds
What are the manifestations of prostate cancer?
urinary frequency, urgency, nocturia, urinary hesitancy, hematuria, hematospermia
What is prostate specific antigen?
PSA is a glycoprotein expressed in normal and neoplastic prostate tissue but usually expressed in higher concentrations in prostate cancer cells
What is the normal value for prostate specific antigen?
0.00- 4.00 ng/ml
Why may a free PSA measurement be used when helping to diagnose prostate cancer?
the ratio of free-to-total PSA is reduced in men with prostate cancer
What is the PSA velocity that is associated with prostate cancer?
> 0.75 ng/mL/year… Serial annual measurement used x 3 years
What are factors that can influence accuracy of PSA tests?
medication, PSA levels change if lab drawn between hour 1-24 after digital recta; exam, recent ejaculation, benign prostatic hyperplasia causes increase PSA in 25% of patients, prostate volume increase with age, increased PSA with age
What are some causes of an increased PSA?
benign prostatic hyperplasia, urinary tract infection, prostate cancer, acute prostatitis, perineal trauma
What can cause a decreased PSA?
medications to treat BPH- finasteride and dutasteride
What are some symptoms of ovarian cancer?
abdominal bloating and distention, pressure near bladder and rectum, constipation, vaginal bleeding, GI symptoms of nausea and vomiting, fatigue, weight loss, early satiety
What is CA125 most present in?
often present in ovarian carcinoma; this test is not recommended as a screening tool currently
Levels of what cancer antigen correspond with level, course and recurrence of ovarian cancer?
CA125
What percent of people with stage 1 ovarian cancer see a positive CA125 result?
50%
What percent of people with stages 2-4 ovarian cancer see a positive result of CA125?
80%
When is CA125 less likely to be elevated?
in obese women
What level of CA125 had a higher predictive value of disease?
over 200 U/ML
What can CA125 be elevated in?
ovarian cancer, breast cancer, colon cancer, liver cancer, pancreatic cancer, lung cancer, hematologic malignancy, many systemic illnesses like infection, autoimmune, cardiac disease
What does OVA-1 use 5 biomarkers to evaluate?
the likelihood that an adnexal mass is cancerous prior to surgery, to identify if a patient with an ovarian mass is high-risk and might need a referral to a gynecologist oncologist, to further manage surgical treatment and follow-up, to identify cancers that were missed by CA125 alone
What are the 5 biomarkers of OVA-1 that are tested?
Beta-2 macroglobulin, CA125II, Apolipoprotein A1, Prealbumin
Beta-2 macroglobulin
tumor marker increased in certain tumors, including ovarian cancer
CA125II
second generation CA125 increased in ovarian and gynecologic tumors
Apolipoprotein A1
involved in cholesterol transport but has some role in tumor suppression
Prealbumin
decreases with tumor burden due to metabolic changes that occur in cancer
Transferrin
down-regulated in ovarian cancer
What is best used to identify epithelia ovarian cancers
OVA1- early stage was 98% sensitivity and late stage was 100% sensitivity
What are the symptoms of colon cancer?
Hematochezia or melena, unexplained weight loss, prolonged diarrhea or constipation, cramping abdominal pain, decrease in size of stool, abdominal distention, gas pain, distention, fullness, vomiting, decreased energy
What is carcinoembryonic antigen (CEA)?
a protein normally found in fetal tissue, levels usually disappear after birth but may be present in colon
Why is CEA not recommended as a screening test?
its sensitivity can vary from 4% in breast cancer to 70+% in colon and rectal cancer
What can cause an increase in CEA?
colon cancer, gastrointestinal tract cancers, breast cancer, ovarian cancer, pancreatic cancer, thyroid cancer, lung cancer, can also be increased in benign conditions such as GI infection or inflammation, even cigarette smoking
What are the symptoms of pancreatic cancer?
abdominal pain, weight loss, jaundice, nausea, vomiting, diarrhea, back pain, dark urine
What is cancer antigen 19-9?
present in epithelial tissues of many organs including the pancreas, stomach, gallbladder, colon… among others
In what cancer is CA 19-9 most frequently used?
pancreatic cancer
What can increase CA 19-9?
pancreatic cancer, gastric cancer, bile duct cancers, colorectal cancers, esophageal cancer, colon cancer, can also be increased
