Review game Flashcards
1
Q
What does the PFA-100 test measure?
A
Closure time for platelet plug
2
Q
A patient has a normal PT, APTT and platelet count but an increased bleeding time. Platelet aggregation studies showed abnormal curves for all aggregating agents – except the ristocetin curve was normal. What is the patient lacking and what is the name of this disorder?
A
GP-IIb/IIIa – Glanzmanns Thrombathenia
3
Q
Why is megakaryocyte hyperplasia of the bone marrow seen in ITP?
A
The immune system is attacking the platelets and this is a healthy bone marrow response.
4
Q
How does thrombopoietin (TPO) work?
A
TPO binds to receptors on platelets and is degraded. Decreased platelets in the blood lead to increased TPO in circulation which stimulates megakaryocyte production.
5
Q
Which disorder is characterized by prolonged bleeding time, giant platelets, and platelet aggregation studies normal with all agents except ristocetin (ristocetin curve is abnormal)?
A
Bernard Soulier
6
Q
In HIT, the antibody is only active in the presence of what substance?
A
Heparin (Heparin-induced thrombocytopenia).
7
Q
What is the antibody associated with HIT/HITTS?
A
It is an Anti-PF4/Heparin complex (IgG)
8
Q
Patient results: bleeding time- increased, APTT- increased, PT- normal, platelet count- normal. Platelet aggregation is normal with all aggregating agents except ristocetin (ristocetin curve is abnormal). To further narrow it down, you’ve added normal donor plasma to the patient PRP. The ristocetin aggregation curve is now normal. What is the most likely diagnosis of this patient?
A
von Willebrands Disease (type I)
9
Q
A patient has the following laboratory findings: thrombocytopenia, MAHA with schistocytes, and fluctuating neurological dysfunction. What other symptom would you expect from this patient?
A
Progressive renal failure (TTP)
10
Q
Name me. Auto-antibodies can be made against me, leading to TTP. I cleave multimers for a living. My mother’s name is Weibel Palade
A
ADAMTS 13
11
Q
Name me. My platelets could go well on a sandwich because they resemble this. Dilation of my platelets’ canicular system leads to a deficient release reaction.
A
Hemansky- Pudlak syndrome – Swiss cheese platelets
12
Q
How do you differentiate between TTP and HUS?
A
TTP- progressive renal failure and neurological symptoms; HUS- acute renal failure and absence of neurological symptoms (possible recent enteric infection)
13
Q
What is the name of the vascular layer made of broad flat endothelial cells?
A
Tunica intima
14
Q
What receptor does vWF adhere to on the platelet and name the disorder in which this receptor is deficient
A
GP-Ib – Bernard Soulier
15
Q
What is the mechanism by which aspirin will affect platelet function
A
Aspirin will inhibit the enzyme Cyclooxygenase, which renders it unable to produce Thromboxane A2 (TXA2). Reduced levels of TXA2 will reduce platelet aggregation.
16
Q
A pregnant woman comes into the ER with a history of preeclampsia, and is experiencing nausea, malaise, and a low platelet count. What might you expect to see on the patient’s peripheral blood smear and why is this significant
A
Schistocytes (rbc fragments) – suspect HELLP syndrome
17
Q
What stimulates shape change in platelets?
A
Platelet activation induced by PLT adhesion
18
Q
How does prostacyclin contribute to vascular function in hemostasis?
A
It normally inhibits platelet adhesion (and is a vasodilator).
19
Q
At what point can platelet activation no longer be reversed?
A
After release reaction (platelets dump contents of granules)
20
Q
What substance is present in the underlying basement membrane of the tunica intima that is important in binding Von Willebrand’s factor.
A
Collagen
21
Q
Describe the phenomena of EDTA clumpers and their possible effect on the patient’s platelet count and white blood cell count?
A
Certain patient’s platelets form clumps when exposed to EDTA. PLT CT= falsely decreased. WBC = falsely increased
22
Q
What is occurring in the infant that is responsible for the pathology of neonatal alloimmune thrombocytopenia?
A
Mother’s antibody is attacking baby’s platelets.
23
Q
Name this disorder: Easy bruising with recent manifestation of many bruises over most of body. Normal PT, Normal APTT, Prolonged bleeding time, Normal platelet count and Normal platelet aggregation studies. No history of bleeding, and has recently begun a dietary cleanse?
A
Scurvy (vitamin C deficiency – decreased synthesis of collagen)
24
Q
Differentiate primary and secondary hemostasis.
A
Primary – platelets aggregate and form plug; Secondary – fibrin develops and strengthens plug
25
Delta storage pool deficiencies are cause by what defect?
Lack of dense granules in platelets
26
Gray platelet syndrome is caused by what defect?
Lack of alpha granules in platelets (results in hypo-granular platelets)
27
Aspirin resistance may be associated with what type of hemostatic disorder?
Thrombosis- 22% of patients become resistant to the antiplatelet effects of aspirin and may actually have increased risk of thrombosis (which can lead to higher risk of MI or stroke
28
The capillary fragility test can be diagnostically significant in what infectious disease?
Dengue Fever
29
What inhibitor forms an irreversible complex with factors IIa, IXa, Xa, XIa, XIIa and plasmin to slowly neutralize them?
AT – antithrombin
30
What are the labile factors of the coagulation cascade and what gives them that name?
V and VIII / short-lived in plasma
31
How is Tissue Plasminogen Activator (TPA) released?
Activated Protein C (APC) causes it to be released from endothelial cells
32
How is Protein C activated?
Thrombin- thrombomodulin complex
33
Bill and Joe stole some prescription drugs from their grandmother’s bathroom medicine cabinet. Thinking the drug warfarin had a rocking name, they took a large dose at the Slayer concert later that night. At the concert, a glass bottle was broken over Joe's head that caused severe lacerations which began bleeding profusely without any sign of stopping. What could potentially counteract the warfarin and bleeding, at least theoretically?
Large dose of Vitamin K – but would not work immediately.
34
Which is the only contact factor that its deficiency causes bleeding?
Factor XI
35
Bill was roughhousing with Joe and his arm was chopped off accidentally. Joe, being a quick wit noticed a bottle of sodium citrate and remembering his hemostasis course quickly dumped it on the wound. Was Joe a genius or a fool and why?
Fool – sodium citrate will bind calcium and acts as an anticoagulant.
36
When is it necessary to adjust the ratio of blood to anticoagulant and what type of adjustment is needed?
When the HCT > 55% - less anticoagulant is needed. Low HCT – more anticoagulant is needed.
37
Name three functions of plasmin.
(5 listed) Break down fibrin and fibrinogen, inactivate Va and VIIIa, degrade XIIa
38
What is the substance needed to convert fibrinogen to fibrin and how does it work to form a clot?
Thrombin cuts off fibrinopeptides A and B from the end of two polypeptide chains. The remaining molecule is a fibrin monomer. These monomers will attach end to end, polymerizing resulting in a fibrin clot.
39
Name two ways Factor (IX) can be activated.
XIa- intrinsic / VIIa, Tissue Factor III and Calcium - extrinsic
40
What are the four components of the Intrinsic Tenase Complex?
Factor VIII, Factor IXa, Calcium ions, and Platelet Factor III.
41
What are the three components of the Extrinsic Tenase Complex?
Tissue factor III, VIIa and Calcium ions
42
Name two roles of the thrombin-thrombomodulin complex
Activate protein C and release Thrombin Activatable Fibrinolytic Inhibitor (TAFI)
43
How does Tissue Factor Pathway Inhibitor work
Inhibition of the extrinsic pathway. Small amount secreted by endothelial cells to inhibit TFIII/ VIIa complex.
44
Plasmin can lyse both fibrin and fibrinogen; fibrinogenolysis is usually harder to achieve, why?
Antiplasmins will destroy most plasmin that escapes the clot.
45
What are the six things activated by Factor IIa?
I, V, VIII, XIII, XI, Protein C
46
Which regulatory substance alters the fibrin clot thus inhibiting fibrinolysis?
Thrombin Activatable Fibrinolytic Inhibitor (TAFI)
47
What mediates the activation of Factor VI
None… no such thing as Factor VI
48
Which normal inhibitor degrades factor Xa and Factor XI?
Protein Z-related Protease Inhibitor (ZPI)
49
Name the coagulation factor that plays a role in both the cascade and platelet aggregation.
Fibrinogen (Factor I)
50
What substance serves as a plasmin inhibitor only when Alpha2 anti-plasmin is depleted?
Alpha2 macroglobulin
51
What substance is released from injured endothelial cells and activated platelets and functions to neutralize TPA?
Plasminogen Activator Inihibitor-1 and 2 (PAI-1 is the most important)
52
Name of 5 of the 7 substances that Factor II acts upon.
Fibrinogen (I)
V
VIII
XI
XIII
Thrombin activatable fibrinolytic inhibitor (TAFI) – II works with thrombomodulin
Protein C – II works with thrombomodulin
53
Name at least 2 exogenous plasminogen activators.
Streptokinase, urokinase, tPA
54
How are Factor V and VIII affected if thrombin fails to act upon them?
They are slow but still work in the coagulation process
55
Thrombin enhances or modifies which coagulation factors?
Factors V and VIII
56
A patient with a bleeding disorder was found to have the following screening test results: PT-normal and APTT- prolonged. What are the possible factor deficiencies?
The patient may be deficient in Factor XI, IX or VIII. The patient is not deficient in Factor XII, because this patient presents with a bleeding disorder. XII deficiencies cause thrombosis.
57
What may happen to coagulation test results if the sodium citrate tube has a short draw?
A short draw can generate erroneously prolonged clot-based test results because there is excess anticoagulant relative to the plasma volume. Excess anticoagulant can have a dilutional effect and may neutralize the calcium in the test reagent.
58
Is Christmas magic?
Of course, Christmas Factor (IX) is part of the Magic 4 clotting factors (II, VII, IX, and X)
59
What are 3 shared traits among the magic 4 coagulation factors?
All produced in the liver
All vitamin K dependent
All depleted by oral anticoagulants
60
Which coagulation factor plays a role in clot formation as well as clot dissolution?
Factor XII
61
How does the presence of FDPs inhibit clotting in coagulation testing?
Interfere with fibrin polymerization
62
A patient is given an excess of urokinase. What would you expect of the PT and APTT results and why?
Both would be increased because plasmin breaks down fibrinogen.
63
What test will determine total fibrinogen levels (including dysfunctional)?
Immunological fibrinogen
64
How do you differentiate HIT from HITTS?
HIT – PLT ct around 100,000 1-3 days after heparin / HITTS – PLT ct as low as 20,000 1-3 days after heparin, as well as thrombosis
65
What does INR stand for and what is its purpose?
International Normalized Ratio: To standardize patient PT results between laboratories
66
How does the Reptilase Time differ from the Thrombin Time?
Reptilase snake venom cleaves only fibrinopeptide A (thrombin cleaves A and B) thus it is not inhibited by routine thrombin inhibitors such as thrombin.
67
Which of the platelet agonists should result in a longer lag phase and a single phase aggregometry graph in 100% of normal subjects after the agent is added to PRP?
Collagen
68
Which test is mostly used to monitor the effects of heparin?
APTT or Anti- Xa activity
69
If a factor XIII deficiency is suspected, what test should be performed and what is the expected result in a deficiency?
Urea clot lysis – clot will lyse < 24 hours
70
A patient has a normal APTT and a prolonged PT. A 50:50 mix was done and the PT was repeated. The PT result was now within the normal reference range. What is the most likely cause of the original abnormal result?
Factor VII deficiency
71
Thrombin time tests for the adequacy of what substance?
Fibrinogen
72
Which procedure will test the common pathway?
Russell viper venom time (RVVT)
73
What test is used to evaluate the body’s fibrinolytic ability?
Euglobulin clot lysis
74
Which phospholipid dependent routine screening test is affected most by the presence of a lupus inhibitor?
APTT
75
How does sodium citrate act as an anticoagulant in the blue top tube and what must be done in many hemostasis tests to overcome this effect?
It binds Ca++, and Ca++ must be added to test plasma to overcome the anticoagulant so it is available to participate in the cascade.
76
Which assay can distinguish between fibrinolysis and fibrinogenolysis? And what are the expected results?
D-dimer: positive in fibrinolysis and negative in fibrinogenolysis
77
What is the advantage of direct factor Xa inhibitors over other antithrombotic therapies?
Doesn’t need to be monitored by lab tests except in special circumstances.
78
What are the possible deficient factors if both the PT and APTT are prolonged?
Factors in the common pathway (X, V, II and I)
79
What does freeze/thawing of donor platelets do in the platelet neutralization procedure?
It ruptures the platelets providing free-floating phospholipid in solution, allowing present APL-Ab to bind platelets, removing them, resulting in a “corrected” time. Used for an initially prolonged DVVT or KCT.
80
In what situation would a 50:50 mix be performed and how would you interpret the results?
If one of the coagulation screening tests (PT, APTT, TT) is prolonged. If the time to clot corrects toward normal - it is a factor deficiency, if there is no significant correction - it is an inhibitor.
81
What is the major difference in reporting for the fibrinogen assay vs. the thrombin time?
Both assays test the conversion of fibrinogen to fibrin by adding thrombin as a reagent. The time for the clot to form is recorded in seconds, but in the fibrinogen assay the time to clot is converted to mg/dL of fibrinogen.
82
Which factor is NOT tested for in routine coagulation screening tests?
Factor XIII
83
In platelet aggregation study, platelet agonist is added. For patient on anti-inflammatory drugs therapy (such as aspirin), what type of pattern is commonly seen?
No secondary phase due to inadequate aggregation
84
List the normal stages of platelet aggregation seen in on a platelet aggregometer?
primary wave of aggregation, release reaction (shoulder) and secondary wave of aggregation
85
What is the primary difference in clot detection using photo-optical vs. mechanical (such as magnetically monitoring) instrumentation?
Photo-optical detects the clot through a change in optical density when the clot forms (the specimen becomes cloudy) vs. mechanical methods detect clot formation by the physical stoppage of a steel ball’s movement (or completion of an electric circuit when a clot is formed)
86
What test (other than a mixing study) can be used to differentiate a lack of fibrinogen from the presence of an inhibitor such as heparin?
Reptilase Time (RT)
87
In platelet aggregation studies, how does ristocetin act differently than the other aggregating agents used?
All other aggregating agents actually initiate platelet aggregation, whereas ristocetin is actually measuring platelet agglutination (platelet sticking to platelet via GP1b and vWF)
88
A patient has a known Factor IX deficiency, but when an MLS conducts a PFA-100, the result falls within the normal reference range. Should it be assumed that the MLS performed the test incorrectly, should it therefore be repeated and why?
The MLS did not perform the test incorrectly and it should not be repeated. The PFA was normal because a Factor IX deficiency does not affect the platelets and platelet function is what is being tested in the PFA.
89
Why is a 50:50 for an APTT read initially and then incubated at 37 degrees for 30 min to 1 hour before they are repeated?
Some inhibitors (such as Factor VIII inhibitor and LI) are time and temperature dependent. Therefore, they may not show their inhibitory effects until they are incubated at 37 for a while.
90
What type of deficiencies would you expect from a patient with no bleeding problems and an increased APTT? Explain this phenomenon.
Possibly Factor XII, Prekallikrein or High Molecular Weight Kininogen deficiency. In the test, APTT is prolonged if these substances are deficient, but in the body, thrombin can make up for these deficiencies because it also activates Factor XI and the rest of the intrinsic pathway. These deficiencies may actually cause thrombosis due to inactivation of plasminogen.
91
What is pNA and in which assay (that we discussed in class) is it used?
pNA stands for Para-nitroalinine, and it is used as a color-producing agent in the Chromogenic Hemostasis Assay. It is used in the Anti-Xa assay. It produces color when cleaved by factor X.
92
Why is it that a prothrombin time, which tests the extrinsic pathway, is unable to test for Tissue Factor III, Calcium or Platelet factor 3?
Because they are added as part of the reagent – Thromboplastin (Neoplastine or Innovin)
93
What is the role of each reagent in the activated partial thromboplastin time?
Activator reagent – substance such as ellagic acid or kaolin mimics the activation of XII by collagen. It also contains phospholipid that acts as a Platelet Factor 3 substitute.
CaCl2 – completes the tenase and prothrombinase complexes (needed in the intrinsic part of the cascade.)
94
A 50-year-old man has been on heparin for the past 7 days. Which of the following test(s) would you expect to be abnormal? PT, APTT, Thrombin time, or fibrinogen assay
PT, APTT and Thrombin Time will be prolonged (PT value will not be as affected as the APTT and TT. The fibrinogen assay will not be affected because the patient specimen is diluted 1:10 before testing)
95
When performing a Factor VIII activity assay, patient plasma is mixed with what substance?
Factor VIII deficient plasma
96
Which Acquired Factor deficiency can be caused by Amyloidosis?
Factor X
97
Which Fibrinogen Disorder would have an abnormal bleeding time
Afibrinogenemia
98
If there is a deficiency of vonWillebrands factor, which other factor will also be affected and why?
Factor VIII, because vWF is a carrier of VIII
99
Why is the bleeding time normal in Hemophilia A?
Factor VIII deficiency will not affect platelet function which is tested in the BT.
100
Even though disseminated intravascular coagulation is a thrombotic process, why is systemic hemorrhage one of the first signs or symptoms?
Many clotting factors are consumed.
101
Prekallekrein deficiency is most often associated with what sort of hemostatic disorder?
Thrombosis – although it is often asymptomatic
102
Bill and Joe’s family have a very rare disease which causes them several problems. Their symptoms include poor would healing, excessive scarring, slow bruise healing, and cranial hemorrhages. Laboratory testing reveals the following: Bleeding time – normal, PT – normal, APTT – normal. What is the most likely hemostatic disorder afflicting this family?
Factor XIII deficiency
103
Hemophilia B is a deficiency of what factor and be the result of the following screening tests (BT, PT, APTT) ?
Factor IX / BT- normal, PT – normal, APTT- prolonged
104
An alpha 2 anti-plasmin deficiency will most likely lead to what sort of hemostatic disorder and why?
Bleeding because plasmin will not be inhibited and it will start to break down the patient’s fibrinogen.
105
Tissue plasminogen activator deficiency causes what type of hemostatic disorder and why?
Thrombosis, because plasminogen is not activated to plasmin resulting in decreased breakdown of fibrin clots.
106
Which pathological or abnormal inhibitor is most often time and temperature dependent and why is knowledge important to testing?
Factor VIII:C inhibitor; must take 50:50 mix results out past immediate testing. Must incubate at 37 for at least 30 min and 1 hour.
107
Which is the rarest congenital factor deficiency?
Prothrombin (II)
108
What is a common complication in hemophilia A patients that have received many doses of Factor VIII concentrate?
Development of a Factor VIII inhibitor
109
Is dysfunctional fibrinogen associated with bleeding or thrombosis?
Both - depending on the defect. In some patients, the defect is that the fibrinogen cannot adequately form a fibrin clot which leads to bleeding. In other patients, the fibrinogen can clot, but the clot formed is resistant to breakdown by plasmin resulting in thrombosis.
110
What disorder is also known as the "royal disease", and is thought to have originated from a random mutation in Queen Victoria? What factor is involved with this disorder?
Hemophilia B
Factor IX
111
For which coagulation factor is lupus inhibitor specific?
None, it is actually an anti-phospholipid antibody
112
What do Anti-cardiolipin Antibody, Lupus Inhibitor and Anti-Beta 2 glycoprotein I all have in common?
They are all anti-phospholipid antibodies.
113
By what mechanism does a Lupus Inhibitor make patients prone to thrombosis?
LI inhibits prostacyclin production or release from endothelial cells which normally inhibits platelets from adhering to healthy endothelium.
114
A patient has no history of bleeding problems but family members have received treatment for thrombosis. Explain why this patient may have an increased APTT.
Factor XII deficiency or heparin therapy. (In vivo thrombin activates factor XI, bypassing factor XII – thus the patient has no bleeding issues, but factor XII is needed for activation of plasminogen to plasmin)
115
Heparins effects can be reversed by administration of what substance?
Protamine sulfate
116
Bill and Joe are playing with some venomous snakes they stole from the zoo. Not being the smartest lads, Bill was bitten when Joe thought it would be funny to hide the snakes in Bill’s boots. Knowing his own limitations in the healing arts, Joe calls you and asks which medicine to administer to reduce thrombosis in his ailing friend. What do you tell him?
Administer heparin, direct Xa inhibitor, or direct thrombin inhibitor. Aspirin will only affect platelets – and not immediately, Warfarin’s affect is also not immediate. (A large bottle of whiskey – won’t help… but probably wouldn’t hurt the situation ;)
117
Why are some patients predisposed to recurrent thrombosis after heparin therapy?
Heparin therapy causes a decrease in the patient’s own Anti-thrombin levels. This is why patients must be slowly weaned off heparin.
118
A young woman has developed swelling in her legs but otherwise seems healthy. Her PT and APTT are normal. Her D-dimer is positive. What medication could be causing her symptoms?
Oral contraceptives
119
How does a Prothrombin mutation (G20210A) cause thrombosis?
Causes increased production of prothrombin.
120
How does a Lupus Inhibitor (lupus anticoagulant) cause thrombosis?
Inhibits prostacyclin that is produced by endothelial cells to inhibit platelet adhesion.
121
Name a drug that can be given to break down a clot.
TPA, urokinase, streptokinase
122
How do the “clot-busting” drugs work to facilitate fibrinolysis?
They convert plasminogen to plasmin and the plasmin then breaks down the clot (or fibrinogen).
123
What is the defect present in patients with Activated Protein C (APC) resistance that causes thrombosis?
Mutant Factor V – Factor V Leiden is resistant to being broken down by Protein C
124
What is the effect of heparin in vivo?
Heparin makes a conformational change in Anti-thrombin which increases its function. AT inactivates thrombin (IIa), Xa, IXa, Xia, XIIa and plasmin.
125
What is an emboli?
A thrombus that has broken free from the original clot site and becomes lodged in capillaries of an organ.
126
How can protein C and protein S deficiencies cause thrombosis?
Factor Va and VIIIa are not inactivated (resulting in more clot formation) and TPA is not released from endothelial cells (thus plasminogen is not converted to plasmin and clots are not broken down)
127
Theoretically, what is the mechanism of thrombosis for defects in homocysteine metabolism (increased homocysteine)?
Increased levels cause damage to endothelial cells
128
Differentiate between primary and secondary fibrinolysis.
Primary – breakdown of fibrinogen
Secondary – breakdown of fibrin
129
What type of hemostatic disorder does a heparin cofactor II deficiency cause? Why does it cause this hemostatic issue?
Thrombosis is caused by a decrease in thrombin neutralization.
