Disorders of Hemostasis

Question 1

___________ refers to the stoppage of blood flow.

Answer 1

hemostasis

Question 2

Hemostasis is divided into three stages:

Answer 2

Vascular constriction
Formation of the platelet plug
Blood coagulation

Question 3

During the process of hemostasis, hairlike __________ strands glue the aggregated platelets together to form the structural basis of the blood clot. In the presence of fibrin, plasma becomes gel-like and traps red blood cells and other formed elements in the blood

Answer 3

fibrin

Question 4

true or false

Hemostasis is complete when fibrous tissue grows into the clot and seals the hole in the vessel.

Answer 4

true

Question 5

Vessel spasm constricts the vessel and reduces blood flow. It is a transient event that usually lasts minutes or hours.2 Vessel spasm is initiated by ____________ ______ and caused by local and humoral mechanisms.

Answer 5

endothelial injury

Question 6

Neural reflexes and _____________ ____, a prostaglandin released from platelets, and other mediators such as serotonin contribute to vasoconstriction.

Answer 6

thromboxane A2

Question 7

The most powerful vasoconstrictor is

Answer 7

endothelin 1

Question 8

____________, another prostaglandin released from the vessel endothelium, produces vasodilation and inhibits platelet aggregation in the surrounding uninjured endothelium.

Answer 8

prostacyclin

Question 9

the __________ ______, the second line of defense, is initiated as platelets come in contact with the vessel wall.

Answer 9

platelet plug

Question 10

platelets, or _____________, are large fragments from the cytoplasm of bone marrow cells called megakaryocytes. The platelet has a half-life of approximately 8 to 12 days, and then it is broken down and eliminated by macrophages.

Answer 10

thrombocytes

Question 11

The normal serum concentration is about _________ to __________ platelets per microliter (µL) of blood.1

Answer 11

150,000 - 400,000

Question 12

Platelet production is controlled by a protein called ___________ that causes proliferation and maturation of megakaryocytes.

Answer 12

thrombopoietin

Question 13

The sources of thrombopoietin include (4)

Answer 13

liver
kidney
smooth muscle
bone marrow

Question 14

Platelets have a cell membrane but no nucleus, and cannot reproduce. The cell membrane has phospholipids that assist with the

Answer 14

coagulation process

Question 15

One of the important glycoproteins is GPIIb/IIIa, which binds __________ and bridges platelets to one another. The platelet shape is maintained by microtubules and actin and myosin filaments that support the cell membrane.

Answer 15

fibrinogen

Question 16

Platelets have mitochondria and enzyme systems capable of producing _________ and _________. They also have the enzymes needed for synthesis of the prostaglandin, TXA2, required for their function in hemostasis.

Answer 16

adenosine triphosphate (ATP)
adenosine diphosphate (ADP)

Question 17

Platelets are attracted to a damaged vessel wall, become activated, and change from smooth disks to spiny spheres, exposing glycoprotein receptors on their surfaces. Platelet adhesion requires a protein molecule called ____ _________ ________, which leaks into the injured tissue from the plasma.

Answer 17

von willed and factor

Question 18

This factor is produced by the endothelial cells of blood vessels and circulates in the blood as a carrier protein for coagulation factor VIII.

Answer 18

von willebrand factor

Question 19

Platelet aggregation occurs soon after adhesion. The secretion of the contents of the platelet granules mediates it. The release of the dense body contents is particularly important because _________ is required for the coagulation component of hemostasis, and ADP is a mediator of platelet aggregation. ADP release also facilitates the release of ADP from other platelets, leading to amplification of the aggregation process.

Answer 19

calcium

Question 20

The combined actions of ADP and TXA2 lead to the expansion of the enlarging platelet aggregate, which becomes the primary hemostatic plug. Stabilization of the platelet plug occurs as the coagulation pathway is activated on the platelet surface and fibrinogen is converted to

Answer 20

fibrin

Question 21

P selectin is also part of the platelet aggregation process since it binds ________, which, with platelet substances such as PDGF, participate in healing of the vessel wall

Answer 21

leukocyte

Question 22

Defective platelet plug formation causes bleeding in people who are deficient in _______ or ______

Answer 22

platelets or vWBF

Question 23

In addition to sealing vascular breaks, platelets play an almost continuous role in maintaining normal vascular integrity. They may supply ______ ______ for endothelial and arterial smooth muscle cells.1 People with platelet deficiency have increased capillary permeability and sustain small skin hemorrhages from the slightest trauma or change in blood pressure.

Answer 23

growth factors

Question 24

Platelet aggregation inhibitors, including (3), can be used to prevent platelet aggregation and clot formation in people who are at risk for myocardial infarction, stroke, or peripheral artery disease.

Answer 24

aspirin, clopidogrel (Plavix), and ticlopidine (Ticlid)

Question 25

how does low dose aspirin work in preventing platelet aggregation?

Answer 25

inhibits prostaglandin synthesis, including TXA2

Question 26

Clopidogrel and ticlopidine achieve their antiplatelet effects by inhibiting the _____ pathway in platelets.

Answer 26

ADP

Question 27

Unlike aspirin, these drugs have an effect on prostaglandin synthesis. Both clopidogrel and ticlopidine

Answer 27

prolong bleeding time

Question 28

clopidogrel and what other class of drugs have been shown to have adverse cardiac effects when used in combination?

Answer 28

PPIs

Question 29

The coagulation cascade is part of the hemostatic process. It is a stepwise process resulting in the conversion of the soluble plasma protein, fibrinogen, into

Answer 29

fibrin

Question 30

Most of the coagulation factors are proteins synthesized in the ______. Vitamin K is necessary for the synthesis of factors II, VII, IX, and X, prothrombin, and protein C.

Answer 30

liver

Question 31

The addition of _______ to blood stored for transfusion purposes prevents clotting by chelating ionic calcium.

Answer 31

citrate

Question 32

The intrinsic pathway, which is a relatively slow process (can cause clotting in 1 to 6 minutes), begins in the circulation with the activation of factor

Answer 32

XII

Question 33

The extrinsic pathway, which is a much faster process (can cause clotting in 15 seconds), begins with trauma to the blood vessel or surrounding tissues and the release of tissue factor or tissue _____________, an adhesive lipoprotein, from the subendothelial cells.

Answer 33

thromboplastin

Question 34

The terminal steps in both intrinsic and extrinsic pathways are the same—the activation of factor ____ and the conversion of prothrombin to thrombin. Thrombin then acts as an enzyme to convert fibrinogen to fibrin, the material that stabilizes a clot.

Answer 34

X

Question 35

The intrinsic system is activated as blood comes in contact with ________ in the injured vessel wall.

Answer 35

collagen

Question 36

The extrinsic system is activated when blood is exposed to

Answer 36

tissue extracts

Question 37

true or false

bleeding that occurs because of defects in the extrinsic system usually is more severe as that resulting from defects in the intrinsic pathway.

Answer 37

false - less severe

Question 38

Protein C, a plasma protein, acts as an anticoagulant by inactivating factors V and VIII. Protein C or PC antigen ala _________ is produced in the liver and prevents thrombosis.

Answer 38

factor V Leiden

Question 39

Protein C deficiency is an inherited defect in factor V and causes increased risk for

Answer 39

clotting

Question 40

Women with factor V Leiden combined with the prothrombotic influence of pregnancy are at high risk for adverse pregnancy outcomes such as (4)

Answer 40

loss
preeclampsia
abruption
venous thromboembolism

Question 41

Protein S, another plasma protein, accelerates the action of protein C. A deficiency of either protein C or S puts one at risk for

Answer 41

thrombosis

Question 42

_________ breaks down fibrin into fibrin degradation products that act as anticoagulants. It has been suggested that some of these natural anticoagulants may play a role in the bleeding that occurs with DIC

Answer 42

plasmin

Question 43

Warfarin acts by decreasing _________ and other procoagulation factors. It alters vitamin K in a manner that reduces its ability to participate in synthesis of the vitamin K–dependent coagulation factors in the liver.

Answer 43

prothrombin

Question 44

Warfarin is readily absorbed after oral administration. Its maximum effect takes ____ to ____ hours because of the varying half-lives of preformed clotting factors that remain in the circulation.

Answer 44

36-72

Question 45

Heparin is naturally formed and released in small amounts by _____ cells in connective tissue surrounding capillaries

Answer 45

mast

Question 46

________ binds to antithrombin III, causing a conformational change that increases the ability of antithrombin III to inactivate thrombin, factor Xa, and other clotting factors. By promoting the inactivation of clotting factors, it ultimately suppresses the formation of fibrin.

Answer 46

heparin

Question 47

because Heparin is unable to cross the membranes of the gastrointestinal tract ….

Answer 47

it must be given by injection

Question 48

Low molecular weight heparins have been developed that inhibit activation of factor X, but have little effect on thrombin and other coagulation factors. The low molecular weight heparins are given by subcutaneous injection and require less frequent administration and

Answer 48

less monitoring

Question 49

There are many potential complications to using warfarin. In addition, the person needs to have frequent laboratory testing of their anticoagulant time with an

Answer 49

International Normalized Ratio (INR) test.

Question 50

A new oral anticoagulant that has less complications and needs less management is dabigatran and is gradually being used with people who have

Answer 50

a fib

Question 51

Clot retraction normally occurs within ___ to ___ _______ after a clot has formed, contributing to hemostasis by squeezing serum from the clot and joining the edges of the broken vessel.

Answer 51

20-60 minutes

Question 52

Clot retraction requires large numbers of platelets, and failure of clot retraction is indicative of a

Answer 52

low platelet count

Question 53

The dissolution of a blood clot begins shortly after its formation. This allows blood flow to be reestablished and permanent tissue repair to take place. The process by which a blood clot dissolves is called

Answer 53

fibrinolysis

Question 54

Plasminogen, the proenzyme for the fibrinolytic process, normally is present in the blood in its inactive form. It is converted into its active form, plasmin, by plasminogen activators formed in the vascular endothelium, liver, and

Answer 54

kidneys

Question 55

_________ __________ _________ (alteplase, reteplase, tenecteplase), produced by recombinant DNA technology, are available for use in treatment of acute myocardial infarction, acute ischemic stroke, and pulmonary embolism.

Answer 55

tissue plasminogen activators

Question 56

______ thrombi are usually due to turbulence and composed largely of platelet aggregates.

Answer 56

arterial

Question 57

_______ thrombi are usually due to stasis of flow and composed largely of platelet aggregates and fibrin complexes that result from activation of the coagulation cascade.

Answer 57

venous

Question 58

The causes of increased platelet function are

Answer 58

disturbances in flow, endothelial damage, and increased sensitivity of platelets to factors that cause adhesiveness and aggregation.

Question 59

Atherosclerotic plaques disturb blood flow, causing endothelial damage and promoting platelet adherence. Platelets that adhere to the vessel wall release _____ _______, which cause proliferation of smooth muscle and thereby contribute to the development of atherosclerosis.

Answer 59

growth factors

Question 60

5 conditions that predispose to vessel damage, platelet adherence, and eventual thrombosis.

Answer 60

smoking 
DM 
hyperlipidemia 
hypercholesterolemia 
hemodynamic stress

Question 61

_________ is used to describe elevations in the platelet count above 1,000,000/µL.

Answer 61

thrombocytosis

Question 62

____________ is the key hormone in the regulation of megakaryocyte differentiation and platelet formation, although various cytokines (e.g., interleukin-6 and interleukin-11) may also play a role.

Answer 62

thrombopoeitin

Question 63

megakaryocyte proliferation and platelet production are normally controlled in a negative feedback mechanism by the ______ count.

Answer 63

platelet

Question 64

The most common cause of secondary thrombocytosis is a disease state that stimulates thrombopoietin production. The common underlying causes of secondary thrombocytosis include

Answer 64

tissue damage due to surgery, infection, cancer, and chronic inflammatory conditions such as rheumatoid arthritis and Crohn disease, polycythemia vera and myelogenous leukemia.

Question 65

thrombopoietin levels are often _______ in essential thrombocytosis, abnormalities in the thrombopoietin receptor and platelet binding cause higher-than-expected levels of free thrombopoietin.

Answer 65

normal

Question 66

The common clinical manifestations of ________ thrombocytosis are thrombosis and hemorrhage.

Answer 66

essential

Question 67

Some people with essential thrombocytosis experience __________, a painful throbbing and burning of the fingers caused by occlusion of the arterioles by platelet aggregates.

Answer 67

erythromelalgia

Question 68

_______ may be a highly effective adjunctive therapy in people with recurrent thrombotic complications.

Answer 68

aspirin

Question 69

Among the acquired or secondary factors that lead to increased coagulation and thrombosis are venous stasis due to

Answer 69

prolonged immobility/bed rest
MI / HF
cancer 
hyperestrogenic states 
oral contraceptives 
smoking 
obesity

Question 70

Slow and disturbed flow is a common cause of venous thrombosis in the immobilized or postsurgical person. It is significant to insure all immobilized people are on _______ therapy, if not contraindicated, in order to prevent deep vein thrombosis and pulmonary embolism.

Answer 70

heparin

Question 71

People with ______ are at high risk for venous and arterial thromboembolism, but also can suffer adverse effects such as gastrointestinal bleeding if anticoagulated.

Answer 71

IBS

Question 72

Hyperviscosity syndromes (polycythemia) and deformed red blood cells in ______ ______ ________ increase the resistance to flow and cause small-vessel stasis

Answer 72

sickle cell disease

Question 73

The incidence of stroke, thromboemboli, and myocardial infarction is greater in women who use oral contraceptives, particularly those older than ____ years of age and those who are heavy smokers

Answer 73

35

Question 74

Clotting factors are also _______ during normal pregnancy. These changes, along with limited activity during the puerperium (immediate postpartum period), predispose to venous thrombosis.

Answer 74

increases

Question 75

__________ also is common in cancer and sepsis. Many tumor cells are thought to release tissue factor molecules, which, along with the increased immobility and sepsis seen in people with malignant disease, contribute to thrombosis in these people.

Answer 75

hypercoagulability

Question 76

Another cause of increased venous and arterial thrombosis is the ________ __________. This condition is associated with autoantibodies (primarily immunoglobulin G [IgG]) directed against protein-binding phospholipids, which results in increased coagulation activity. The common features are venous and arterial thrombi, recurrent fetal loss, and thrombocytopenia.

Answer 76

antiphospholipid syndrome

Question 77

antiphospholipid syndrome can be a primary condition occurring in isolation with signs of hypercoagulability or a secondary condition sometimes associated with

Answer 77

lupus

Question 78

In most people with __________ ________, the thrombotic events occur as a single episode at one anatomic site. In some people, recurrences may occur months or years later and mimic the initial event. Occasionally, someone may present with multiple vascular occlusions involving many organ systems.

Answer 78

antiphospholipid syndrome

Question 79

Bleeding due to platelet disorders reflects a decrease in platelet number due to decreased production, increased destruction, or impaired function of platelets. Spontaneous bleeding from platelet disorders most often involves small vessels of the

Answer 79

mucous membranes and skin

Common sites of bleeding are the mucous membranes of the nose, mouth, gastrointestinal tract, and uterine cavity.

Question 80

Cutaneous bleeding is seen as pinpoint hemorrhages (petechiae) and purple areas of bruising (purpura) in dependent areas where the capillary pressure is higher. Petechiae are seen almost exclusively in conditions of platelet ______ and not platelet dysfunction.

Answer 80

deficiency

Question 81

Thrombocytopenia usually refers to a decrease in the number of circulating platelets to a level less than

Answer 81

150,000

Question 82

Decreased platelet production due to loss of bone marrow function occurs in

Answer 82

aplastic anemia

Question 83

Radiation therapy and drugs such as those used in the treatment of cancer may depress bone marrow function and ______ platelet production. Infection with human immunodeficiency virus (HIV) or cytomegalovirus may suppress the production of megakaryocytes, the platelet precursors.

Answer 83

reduce

Question 84

Production of platelets may be normal, but excessive pooling of platelets in the spleen may occur. Although the spleen normally sequesters 30% to 40% of the platelets before release into the circulation, the proportion can be as great as 90% when the spleen is enlarged in splenomegaly.1 When necessary, hypersplenic thrombocytopenia may be treated with

Answer 84

splenectomy

Question 85

Reduced platelet survival is caused by a variety of immune and nonimmune mechanisms. Platelet destruction may be caused by antiplatelet antibodies. The antibodies may be directed against platelet self-antigens or against antigens on the platelets from ______ ________ or ___________

Answer 85

blood transfusion

pregnancy

Question 86

Nonimmune destruction of platelets results from mechanical injury due to ______ ______ ________ or _________ ________, which results in small-vessel narrowing.

Answer 86

prosthetic heart valves

malignant hypertension

Question 87

In acute ____ or thrombotic thrombocytopenic purpura, excessive platelet consumption leads to a deficiency.

Answer 87

DIC

Question 88

some drugs such as (3) may induce thrombocytopenia.4 These drugs induce an antigen–antibody response and formation of immune complexes that cause platelet destruction by complement-mediated lysis. In people with drug-associated thrombocytopenia, there is a rapid fall in the platelet count within 2 to 3 days of resuming a drug or 7 or more days (i.e., the time needed to mount an immune response) after starting a drug for the first time. The platelet count rises rapidly after the drug is discontinued.

Answer 88

quinine
quinidine
certain sulfa containing antibiotics

Question 89

is associated with the anticoagulant drug heparin. Ten percent of people treated with heparin develop a mild, transient thrombocytopenia within 2 to 5 days of starting the drug. However, approximately 1% to 5% of people treated with heparin experience life-threatening thromboembolic events 1 to 2 weeks after the start of therapy

Answer 89

heparin induced thrombocytopenia

Question 90

_____ is caused by an immune reaction directed against a complex of heparin and platelet factor 4, a normal component of platelet granules that binds tightly to heparin. The binding of antibody to platelet factor 4 produces immune complexes that activate the remaining platelets, leading to thrombosis. In addition, prothrombotic platelet particles and induction of tissue factor continue to promote coagulation.

Answer 90

HIT

Question 91

treatment of HIT

Answer 91

d.c. heparin and start alternative anticoagulant

The newer low molecular weight heparin has been shown to be effective in reducing the incidence of heparin-induced complications compared with the older, high molecular weight form of the drug.

Question 92

_________ autoimmune disorder, results in platelet antibody formation and excess destruction of platelets.

Answer 92

immune thrombocytopenic purpura

Question 93

The disorder can occur in the absence of any known risk factors (primary) or as a secondary disorder due to an underlying disorder and as an acute (duration of 6 months or less) or chronic disorder. Secondary forms of ____ may be associated with acquired immunodeficiency syndrome (AIDS), systemic lupus erythematosus, antiphospholipid syndrome, chronic lymphocytic leukemia, lymphoma, hepatitis C, and drugs such as heparin and quinidine.

Answer 93

ITP

Question 94

An acute ITP disorder occurs in young children (5 years of age) and usually follows ______ _______

Answer 94

viral infection

Question 95

It is characterized by sudden onset of petechiae and purpura in children under 5 years of age and is usually a self-limited disorder requiring no treatment. Most children recover in a few weeks.

Answer 95

acute ITP

Question 96

Evidence suggests that ITP is caused by ___-cell dysfunction, specifically CD4 and T regulatory cells, which trigger the autoimmune response and proceed to thrombocytopenia.

Answer 96

T cell

Question 97

true or false

The decision to treat ITP is based on the platelet count and the degree of bleeding. Many persons with ITP do well without treatment.

Answer 97

true

Question 98

treatment of ITP

_____________ are usually used as initial therapy. Other effective initial treatments include intravenous immune globulin. However, this treatment is expensive, and the beneficial effect lasts only 1-2 weeks

Answer 98

corticosteroids

Question 99

The clinical manifestations include purpura, petechiae, vaginal bleeding, and neurologic symptoms ranging from headache to seizures and altered consciousness.

Answer 99

TTP

Question 100

Emergency treatment for TTP includes _______, a procedure that involves removal of plasma from withdrawn blood and replacement with fresh-frozen plasma.

Answer 100

plasmaphoresis

Question 101

Impaired platelet function (also called ____________) may result from inherited disorders of adhesion (e.g., von Willebrand disease) or acquired defects caused by drugs, disease, or surgery involving extracorporeal circulation (i.e., cardiopulmonary bypass). Defective platelet function is also common in uremia, presumably because of unexcreted waste products.

Answer 101

thrombocytopathia

Question 102

The use of _____ and other ______ is the most common cause of impaired platelet function.

Answer 102

apirin and NSAIDs

Question 103

____ is considered the most frequent inherited coagulopathy and affects approximately 1% to 2% of the population

Answer 103

vWB disease

Question 104

Hemophilia A (factor ___ deficiency) affects 1 in 5000 male live births.

Answer 104

VIII

Question 105

Hemophilia B (factor __ deficiency) occurs in approximately 1 in 20,000 people, accounting for 15% of people with hemophilia.

Answer 105

IX

Question 106

vWF, which is synthesized by the _______ and ___________, is required for platelet adhesion to the subendothelial matrix of the blood vessel. It also serves as the carrier for factor VIII and is important for the stability of factor VIII in the circulation by preventing its proteolysis.

Answer 106

endothelium and megakaryocytes

Question 107

three types of vWB disease. types 1 and 2 are autosomal ________ while type 3 is autosomal _______

Answer 107

1 and 2 - dominant

3 - recessive

Question 108

Hemophilia A is an X-linked recessive disorder that primarily affects

Answer 108

males

Question 109

Although it is a hereditary disorder, there is no family history of the disorder in approximately 30% of newly diagnosed cases, suggesting that it has arisen as a new mutation in the factor VIII gene.

Answer 109

hemophilia A

Question 110

In severe hemophilia, bleeding usually occurs in childhood (e.g., it may be noticed at the time of _________) and is spontaneous and severe, often occurring several times a month.

Answer 110

circumcision

Question 111

Characteristically, bleeding in hemophilia A occurs in soft tissues, the gastrointestinal tract, and the hip, knee, elbow, and ankle joints. Spontaneous joint bleeding usually begins when a child begins to

Answer 111

walk

Question 112

_____ begins with massive activation of the coagulation sequence as a result of unregulated generation of thrombin, resulting in systemic formation of fibrin. In addition, levels of all the major anticoagulants are reduced. The microthrombi that result cause vessel occlusion and tissue ischemia. Multiple organ failure may ensue. Clot formation consumes all available coagulation proteins and platelets, and severe hemorrhage results.

Answer 112

DIC