Disorders of Hemostasis Flashcards
___________ refers to the stoppage of blood flow.
hemostasis
Hemostasis is divided into three stages:
Vascular constriction
Formation of the platelet plug
Blood coagulation
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
fibrin
true or false
Hemostasis is complete when fibrous tissue grows into the clot and seals the hole in the vessel.
true
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.
endothelial injury
Neural reflexes and _____________ ____, a prostaglandin released from platelets, and other mediators such as serotonin contribute to vasoconstriction.
thromboxane A2
The most powerful vasoconstrictor is
endothelin 1
____________, another prostaglandin released from the vessel endothelium, produces vasodilation and inhibits platelet aggregation in the surrounding uninjured endothelium.
prostacyclin
the __________ ______, the second line of defense, is initiated as platelets come in contact with the vessel wall.
platelet plug
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.
thrombocytes
The normal serum concentration is about _________ to __________ platelets per microliter (µL) of blood.1
150,000 - 400,000
Platelet production is controlled by a protein called ___________ that causes proliferation and maturation of megakaryocytes.
thrombopoietin
The sources of thrombopoietin include (4)
liver
kidney
smooth muscle
bone marrow
Platelets have a cell membrane but no nucleus, and cannot reproduce. The cell membrane has phospholipids that assist with the
coagulation process
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.
fibrinogen
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.
adenosine triphosphate (ATP) adenosine diphosphate (ADP)
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.
von willed and factor
This factor is produced by the endothelial cells of blood vessels and circulates in the blood as a carrier protein for coagulation factor VIII.
von willebrand factor
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.
calcium
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
fibrin
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
leukocyte
Defective platelet plug formation causes bleeding in people who are deficient in _______ or ______
platelets or vWBF
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.
growth factors
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.
aspirin, clopidogrel (Plavix), and ticlopidine (Ticlid)
how does low dose aspirin work in preventing platelet aggregation?
inhibits prostaglandin synthesis, including TXA2
Clopidogrel and ticlopidine achieve their antiplatelet effects by inhibiting the _____ pathway in platelets.
ADP
Unlike aspirin, these drugs have an effect on prostaglandin synthesis. Both clopidogrel and ticlopidine
prolong bleeding time
clopidogrel and what other class of drugs have been shown to have adverse cardiac effects when used in combination?
PPIs
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
fibrin
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.
liver
The addition of _______ to blood stored for transfusion purposes prevents clotting by chelating ionic calcium.
citrate
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
XII
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.
thromboplastin
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.
X
The intrinsic system is activated as blood comes in contact with ________ in the injured vessel wall.
collagen
The extrinsic system is activated when blood is exposed to
tissue extracts
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.
false - less severe
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.
factor V Leiden
Protein C deficiency is an inherited defect in factor V and causes increased risk for
clotting
Women with factor V Leiden combined with the prothrombotic influence of pregnancy are at high risk for adverse pregnancy outcomes such as (4)
loss
preeclampsia
abruption
venous thromboembolism
Protein S, another plasma protein, accelerates the action of protein C. A deficiency of either protein C or S puts one at risk for
thrombosis
_________ 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
plasmin
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.
prothrombin
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.
36-72
Heparin is naturally formed and released in small amounts by _____ cells in connective tissue surrounding capillaries
mast
________ 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.
heparin
because Heparin is unable to cross the membranes of the gastrointestinal tract ….
it must be given by injection
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
less monitoring
There are many potential complications to using warfarin. In addition, the person needs to have frequent laboratory testing of their anticoagulant time with an
International Normalized Ratio (INR) test.
A new oral anticoagulant that has less complications and needs less management is dabigatran and is gradually being used with people who have
a fib
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.
20-60 minutes
Clot retraction requires large numbers of platelets, and failure of clot retraction is indicative of a
low platelet count
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
fibrinolysis
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
kidneys
_________ __________ _________ (alteplase, reteplase, tenecteplase), produced by recombinant DNA technology, are available for use in treatment of acute myocardial infarction, acute ischemic stroke, and pulmonary embolism.
tissue plasminogen activators
______ thrombi are usually due to turbulence and composed largely of platelet aggregates.
arterial
_______ 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.
venous
The causes of increased platelet function are
disturbances in flow, endothelial damage, and increased sensitivity of platelets to factors that cause adhesiveness and aggregation.
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.
growth factors
5 conditions that predispose to vessel damage, platelet adherence, and eventual thrombosis.
smoking DM hyperlipidemia hypercholesterolemia hemodynamic stress
_________ is used to describe elevations in the platelet count above 1,000,000/µL.
thrombocytosis
____________ 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.
thrombopoeitin
megakaryocyte proliferation and platelet production are normally controlled in a negative feedback mechanism by the ______ count.
platelet
The most common cause of secondary thrombocytosis is a disease state that stimulates thrombopoietin production. The common underlying causes of secondary thrombocytosis include
tissue damage due to surgery, infection, cancer, and chronic inflammatory conditions such as rheumatoid arthritis and Crohn disease, polycythemia vera and myelogenous leukemia.
thrombopoietin levels are often _______ in essential thrombocytosis, abnormalities in the thrombopoietin receptor and platelet binding cause higher-than-expected levels of free thrombopoietin.
normal
The common clinical manifestations of ________ thrombocytosis are thrombosis and hemorrhage.
essential
Some people with essential thrombocytosis experience __________, a painful throbbing and burning of the fingers caused by occlusion of the arterioles by platelet aggregates.
erythromelalgia
_______ may be a highly effective adjunctive therapy in people with recurrent thrombotic complications.
aspirin
Among the acquired or secondary factors that lead to increased coagulation and thrombosis are venous stasis due to
prolonged immobility/bed rest MI / HF cancer hyperestrogenic states oral contraceptives smoking obesity
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.
heparin
People with ______ are at high risk for venous and arterial thromboembolism, but also can suffer adverse effects such as gastrointestinal bleeding if anticoagulated.
IBS
Hyperviscosity syndromes (polycythemia) and deformed red blood cells in ______ ______ ________ increase the resistance to flow and cause small-vessel stasis
sickle cell disease
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
35
Clotting factors are also _______ during normal pregnancy. These changes, along with limited activity during the puerperium (immediate postpartum period), predispose to venous thrombosis.
increases
__________ 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.
hypercoagulability
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.
antiphospholipid syndrome
antiphospholipid syndrome can be a primary condition occurring in isolation with signs of hypercoagulability or a secondary condition sometimes associated with
lupus
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.
antiphospholipid syndrome
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
mucous membranes and skin
Common sites of bleeding are the mucous membranes of the nose, mouth, gastrointestinal tract, and uterine cavity.
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.
deficiency
Thrombocytopenia usually refers to a decrease in the number of circulating platelets to a level less than
150,000
Decreased platelet production due to loss of bone marrow function occurs in
aplastic anemia
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.
reduce
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
splenectomy
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 ___________
blood transfusion
pregnancy
Nonimmune destruction of platelets results from mechanical injury due to ______ ______ ________ or _________ ________, which results in small-vessel narrowing.
prosthetic heart valves
malignant hypertension
In acute ____ or thrombotic thrombocytopenic purpura, excessive platelet consumption leads to a deficiency.
DIC
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.
quinine
quinidine
certain sulfa containing antibiotics
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
heparin induced thrombocytopenia
_____ 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.
HIT
treatment of HIT
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.
_________ autoimmune disorder, results in platelet antibody formation and excess destruction of platelets.
immune thrombocytopenic purpura
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.
ITP
An acute ITP disorder occurs in young children (5 years of age) and usually follows ______ _______
viral infection
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.
acute ITP
Evidence suggests that ITP is caused by ___-cell dysfunction, specifically CD4 and T regulatory cells, which trigger the autoimmune response and proceed to thrombocytopenia.
T cell
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.
true
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
corticosteroids
The clinical manifestations include purpura, petechiae, vaginal bleeding, and neurologic symptoms ranging from headache to seizures and altered consciousness.
TTP
Emergency treatment for TTP includes _______, a procedure that involves removal of plasma from withdrawn blood and replacement with fresh-frozen plasma.
plasmaphoresis
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.
thrombocytopathia
The use of _____ and other ______ is the most common cause of impaired platelet function.
apirin and NSAIDs
____ is considered the most frequent inherited coagulopathy and affects approximately 1% to 2% of the population
vWB disease
Hemophilia A (factor ___ deficiency) affects 1 in 5000 male live births.
VIII
Hemophilia B (factor __ deficiency) occurs in approximately 1 in 20,000 people, accounting for 15% of people with hemophilia.
IX
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.
endothelium and megakaryocytes
three types of vWB disease. types 1 and 2 are autosomal ________ while type 3 is autosomal _______
1 and 2 - dominant
3 - recessive
Hemophilia A is an X-linked recessive disorder that primarily affects
males
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.
hemophilia A
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.
circumcision
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
walk
_____ 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.
DIC
