Heme Flashcards
(169 cards)
1
Q
Heinz bodies (inclusions within red blood cells composed of denatured hemoglobin)
A
G6PD deficiency, Alpha-thalassemia
2
Q
Spherocytes (Due to underlying pathology, blood cell contracts to its most surface-tension efficient and least flexible configuration, a sphere)
A
Hereditary spherocytosis and autoimmune hemolytic anemia
3
Q
Elliptocytes
A
Very often seen in Iron deficiency (also could be seen in Thalassemia, Myelophthisic anemias, and Megaloblastic anemias)
4
Q
Target Cells (seen on a peripheral blood smear when there is excess membrane relative to the amount of hemoglobin)
A
Membrane may be excessive in liver disease. Intracellular hemoglobin may be lowered during iron deficiency, thalassemia, hemoglobin C or SC and other hemoglobinopathies.
5
Q
Teardrop Cells/dacrocytes (a type of poikilocyte that is shaped like a teardrop)
A
Myelofibrosis and myelophthisic anemia
6
Q
Schistocytes (fragmented parts of red blood cells)
A
Microangiopathic Hemolytic Anemia
7
Q
Bite Cells (result from the removal of denatured hemoglobin by macrophages in the spleen)
A
G6PDH deficiency
8
Q
Echinocytes (red blood cells that have a spiked cell membrane, due to abnormal thorny projections)
A
Can be due to an osmotic abnormality in liver disease, kidney disease
9
Q
Howell-Jolly bodies (Nuclear remnants)
A
Splenectomy
10
Q
Basophilic stippling (Clumped ribosomes in RBCs that are more severe than in reticulocytes, and can be seen without special stain)
A
Lead poisoning (coarse stippling) and Thalassemia. Not seen in Iron deficiency
11
Q
Pappenheimer bodies (iron granules in RBCs)
A
Non specific finding that could be seen in Sideroblastic anemia, hemolytic anemia, and sickle cell disease
12
Q
Hemoglobin C crystals
A
Homozygous hemoglobin C
13
Q
Cytokine receptor tyrosine kinase, expressed on the surface of many hematopoietic progenitor cells, that binds ligand on the outside of the cell. Activating mutations in what are found in 41% of AML
A
Flt-3
14
Q
A receptor tyrosine kinase for stem cell factor that binds ligand on the outside of the cell. Activating mutations in what are found in certain AML subtypes (“core binding factor leukemias), systemic mastocytosis, and GI stromal tumors (inhibited by imatinib)
A
C-Kit
15
Q
A family of cell surface receptors that function in cell fate determination during embryogenesis in multiple tissues that is frequently mutated in T cell ALL
A
Notch
16
Q
Recognizes ligands such as jagged, delta, and delta-like on adjacent cells.
A
Notch
17
Q
Signaling involves proteolysis by gamma-secretase and translocation to the nucleus. Signaling promotes pluripotent stem cell survival, specifies lymphoid lineage over myeloid differentiation, and specifies T cell over B cell lineage in common lymphoid progenitors
A
Notch
18
Q
Mutations of what are found in more than 50% of human T cell lymphoblastic leukemia
A
Notch
19
Q
What normally degrades hypoxia-inducible factor (HIF) but stops degrading it in hypoxic conditions.
A
Von Hippel Lindau
20
Q
Hypoxia-inducible factor (HIF) activates what
A
Erythropoietin (EPO)
21
Q
EPO binds which receptor
A
JAK receptor
22
Q
JAK phosphorylates
A
STAT
23
Q
What does STAT do
A
Activates transcription
24
Q
What is often deleted in renal clear cell carcinomas and what is the consequence
A
Von Hippel-Lindau protein is deleted. Without VHL, HIF will not be degraded and will be free to activate erythropoiesis. Therefore, some patients with renal cell carcinomas develop secondary polycythemia (the proportion of blood volume that is occupied by red blood cells increases)
25
Automated blood analysis of Hb
lyse cells, measure spectrophotometrically. The more hemoglobin, the less light passes through
26
Cell counting is done by
Flow cytometry
27
In hydrodynamic focusing, cells line up in mid stream and light scatter or electrical impedance is measured. What do forward and side scatter indicate
Forward scatter is a measure of size, side scatter is a measure of internal complexity
28
A family of single-pass transmembrane proteins that show expression on early hematopoietic and vascular-associated tissue
CD34
29
CD34+, multipotent, self-renewing cells
Pluripotent hematopoietic stem cells
30
CD34+, partially differentiated/usually unipotent cell (has lost most or all of the stem cell multipotency)
Blast cell
31
Quiescent, non-dividng state of pluripotent hematopoietic stem cells is reflected by the expression of
cyclin-dependent kinase inhibitors
32
Definitive hematopoiesis produces
Smaller cells that express only adult hemoglobins
33
4/5 of CSF receptors signal through
JAK/STAT pathway
34
Produced by renal interstitial cells in response to hypoxia by hypoxia inducible factor (HIF)
Erythropoietin (EPO)
35
Prevents apoptosis of erythroid progenitors
Erythropoietin (EPO)
36
Mutation in a cytoplasmic (non-receptor) tyrosine kinase, JAK-2, which transduces the EPO signal, is found in almost all cases of
Polycythemia vera
37
Produces hypochlorite from peroxide, and is the most specific marker of myeloid differentiation (as apposed to lymphoid or erythroid)
Myeloperoxidase
38
Measure of the average red blood cell size
Mean corpuscular volume (MCV)
39
Measure of the concentration of hemoglobin in a given volume of packed red blood cells
Mean corpuscular hemoglobin concentration (MCHC)
40
Variability in RBC size
RBC distribution width (RDW)
41
Increase in abnormal red blood cells of any shape where they make up 10% or more of the total population
Poikilocytosis
42
Heme is turned into unconjugated bilirubin where
In the reticuloendothelial cells of the spleen
43
Not soluble in water, due to intramolecular hydrogen bonding. It is then bound to albumin and sent to the liver.
Unconjugated bilirubin
44
Bilirubin is conjugated with what, making it soluble in water
Glucuronic acid
45
What binds free hemoglobin (Hb) released from erythrocytes with high affinity and thereby inhibits its oxidative activity
Haptoglobin
46
The haptoglobin-hemoglobin complex will then be removed by
The reticuloendothelial system (mostly the spleen)
47
What is abundant in red blood cells and can function as a marker for hemolysis
Lactate dehydrogenase (LDH)
48
In clinical settings, what is used to screen for and monitor intravascular hemolytic anemia
The haptoglobulin assay (In intravascular hemolysis, free hemoglobin will be released into circulation and hence haptoglobin will bind the Hb)
49
Inclusions within red blood cells composed of denatured hemoglobin. They are formed by damage to the hemoglobin component molecules, usually through oxidant damage, or from an inherited mutation
Heinz bodies
50
The presence in the blood of erythrocytes of varying sizes and abnormal shapes
Anisopoikilocytosis
51
CD55
DAF: regulates the complement system on the cell surface
52
CD59
MIRL: inhibits the complement membrane attack complex
53
Indirect Coombs test
Used to detect in-vitro antibody-antigen reactions. It is used to detect very low concentrations of antibodies present in a patient's plasma/serum prior to a blood transfusion. In antenatal care, the IAT is used to screen pregnant women for antibodies that may cause hemolytic disease of the newborn. The IAT can also be used for compatibility testing, antibody identification, RBC phenotyping, and titration studies
54
Direct Coombs test
Used to detect if antibodies or complement system factors have bound to RBC surface antigens in vivo
55
Diagnosis of autoimmune and some forms of drug-induced hemolytic anemia. Evalutation of hemolytic transfusion reactions. Diagnosis of hemolytic disease of newborn.
Direct Coombs test (Direct antiglobulin test)
56
Detection of incomplete (noncoaggulatinating) antibodies in patient with hemolytic anemia or in patient's serum to potential donor RBCs (or to screening cells. Determination of RBC phenotype using known anti-sera to specific blood group antigens. Titration of allo-anti-D in Rh-negative pregnant women
Indirect Coombs test (Indirect antiglobulin test)
57
Packed RBCs
Usual component for RBC therapy that is prepared by centrifugation of the WB donation which removes most of the plasma. It is stored at 4 degrees C (storage life is 35 days).
58
Fresh Frozen Plasma
After removal of the RBC fraction of the whole blood donation, the platelet-rich plasma then subjected to a "hard" centrifugation to remove the platelets and most WBCs to form "platelet-poor" plasma.
59
Random donor and single donor platelets
Whole blood donation (random donor) or apheresis (single donor). Platelets stored at 22-24 degrees C (storage life is 5 days).
60
Cryoprecipitate
Cryoprecipitated Antihaemophilic Factor: The cold-precipitated concentration of Factor VIII (the 'antihemophilic factor" AHF). Just prior to transfusion, CRYO is quick-thawed at 37 degrees C and is pooled with other units. Storage of 12 months in frozen state, 6 hr once thawed, and 4 hours once pooled
61
Apheresis
A process by which whole blood is removed from the donor by a closed-system instrument which houses a centrifuge that separates the blood components, selectively removes the desired component, and then recombines the remaining components for return to the donor
62
Occurs very soon after transfusion of incompatible RBCs
IHTR - immediate hemolytic transfusion reaction
63
Antibodies causing IHTRs bind complement to the RBC surface and have efficient in vitro lytic properties. RBC destruction occur primarily by intravascular hemolysis. The 4 most commonly identified RBC antibodies causing IHTRs are
Antio-A, Anti-kell, Anti-kidd a, and anti-duffy a
64
Signs and symptoms: IHTR
Fever with/without chills, oliguria, DIC or coagulopathy, hypotension
65
The majority of IHTRs are caused by
Clerical error, they are potentially preventable
66
Noncardiogenic pulmonary edema reactions associated with transfusion. Recent sweeping changes that could affect 10-20% of female donors
TRALI - transfusion related acute lung injury
67
Signs and symptoms: TRALI
Chills, cough, fever, cyanosis, hypotension, and increasing respiratory distress shortly after transfusion.
68
Least common AIHA, more common in children than other types in association with viral illnesses, dramatic clinical presentation: acute paroxysmal or intermittent episodes of hemoglobinuria upon exposure to cold.
Paroxysmal cold hemoglobinuria
69
What antibody screen and crossmatch is needed before transfusion
ABO/Rh
70
A blood transfusion condition that occurs due to a rapid transfusion of a large volume of blood.
TACO - transfusion related circulatory overload
71
The primary symptoms of TACO are
Dyspnea, orthopnea, peripheral edema, and rapid increase of blood pressure
72
TACO differs from Transfusion related acute lung injury (TRALI)
By having longer hospital stays and increased morbidity
73
TA-GVHD - transfusion-associated graft versus host disease can develop how many days after the transfusion
4-30 days
74
a rare complication of blood transfusion, in which the donor T lymphocytes mount an immune response against the recipient's lymphoid tissue
TA-GVHD - transfusion-associated graft versus host disease
75
Typical symptoms: TA-GVHD - transfusion-associated graft versus host disease
Fever, erythematous maculopapular rash (which can progress to generalised erythroderma), toxic epidermal necrolysis in extreme cases, cough, abdominal pain, vomiting, and profuse diarrhea
76
a biochemical technique used to detect a virus or a bacterium. These tests were developed to shorten the window period, a time between when a patient has been infected and when they show up as positive by antibody tests
NAT -nucleic acid testing
77
Most common cause of transfusion-associated fatalities (usually a clerical error resulting in a recipient receiving the wrong blood type)
AHTR - acute hemolytic transfusion reaction
78
Occurs about 3-7 days after transfusion. An anamnestic response from previous sensitization from previous pregnancy, transfusion or transplant. Antibody not detected in routine pretransfusion testing. RBC destruction occurs primarily by extravascular hemolysis.
DHTR - delayed hemolytic transfusion reaction
79
Signs and symptoms: DHTR - delayed hemolytic transfusion reaction
Milder compared to IHTR and is commonly subclinical (usually mild fever or fever with chills and/or mild to moderate jaundice). Only treatment for asymptomatic anemia: monitor patient to reduce risk of renal failure.
80
Immediate or delayed. Most often occur with transfusion of ABO-incompatible RBCs (AB-incompatible plasma-containing products or chemical/physical injury). May be stimulated by a number of diseases
Acute and delayed HTRs
81
One of the most common transfusion reactions. 1 degree C (2 degrees F) rise in temperature associated during or shortly after transfusion and having no other explanation
Febrile nonhemolytic transfusion reactions (FNHTR).
82
Signs and symptoms: Febrile nonhemolytic transfusion reactions (FNHTR).
Fever with chills and hypotension (usually mild), severe reactions can rarely occur and mimic sepsis.
83
One of the most common transfusion reactions. Appear within minutes of transfusion and represent mild immediate hypersensitivity type immune reactions to plasma proteins
Allergic reaction
84
Moderate to severe immediate hypersensitivity type immune reactions. Two significant features distinguish these reactions from other types of transfusion reactions: Fever is absent, and signs/symptoms occur after transfusion of just a few mls of plasma or plasma-containing component
Anaphylactic reaction
85
A type of anaphylaxis that does not involve an allergic reaction but is due to direct mast cell degranulation. Usually less severe
Anaphylactoid reaction
86
Majority are mild, most reported as FNHTR. Local erythema, prusitis, hives. Can rarely be more severe.
Allergic reaction
87
Coughing, dyspnea, nausea, vomiting, bronchospasm, chest pain, hypotension, diarrhea, and shock. Occurs in IgA-deficient patients who have class-specific anti-IgA. IgA deficiency is relatively common but the incidence of this is low
Anaphylactic reaction
88
Urticaria, periorbital edema, dyspnea, and laryngeal edema. Occurs in patients with decreased or normal levels of IgA with a limited type-specific anti-IgA antibody that reacts with the light chain fragment of the donor's IgA.
Anaphylactoid reaction
89
The single most important transfusion-transmitted infection
HCV
90
Methylmalonyc CoA mutase requires B12 but not folate and catalyzes what reaction
Methylmalonyl CoA to succinyl CoA
91
Serum folate reflects recent folate (may be normal in deficient patient who has had recent intake). What is a better reflection of tissue folate levels.
Red cell folate
92
What refers to the presence of nucleated red blood cells and primitive white blood cells. It is seen in bone marrow failure, myelofibrosis and extramedullary haemopoiesis.
Leukoerthyroblastic change
93
Measures of the extrinsic pathway of coagulation
Prothrombin time (PT)
94
PT measures which factors
I (fibrinogen), II (thrombin), V, VII, and X.
95
Used to determine the clotting tendency of blood, in the measure of warfarin dosage, liver damage, and vitamin K status.
Prothrombin time (PT)
96
Performance indicator measuring the efficacy of both the "intrinsic" (now referred to as the contact activation pathway) and the common coagulation pathways.
Activated partial thromboplastin time (APTT). Also called PTT
97
Apart from detecting abnormalities in blood clotting, it is also used to monitor the treatment effects with heparin, a major anticoagulant.
Activated partial thromboplastin time (APTT). Also called PTT
98
PTT measures which factors
I, II, V, VIII, IX, X, XI, & XII (Notably, deficiencies in factors VII or XIII will not be detected with the PTT test)
99
Heparin-induced thrombocytopenia (HIT) is caused by
The formation of abnormal antibodies that activate platelets.
100
The receptor for von Willebrand factor that is important in clot formation.
glycoprotein Ib (GpIb)
101
A rare autosomal recessive coagulopathy (bleeding disorder) that causes a deficiency of glycoprotein Ib (GpIb)
Bernard-Soulier syndrome
102
Glycoprotein IIb/IIIa (GpIIb/IIIa) is a receptor for what
Fibrin/Fibrinogen
103
An abnormality of platelets. It is an extremely rare coagulopathy (bleeding disorder due to a blood abnormality), in which the platelets contain defective or low levels of glycoprotein IIb/IIIa (GpIIb/IIIa), resulting in no fibrin/fibrinogen bridging of platelets to other platelets can occur, and the bleeding time is significantly prolonged.
Glanzmann's thrombasthenia
104
An ex vivo assay for live platelet function. Exogenous antibiotic is added in a graded fashion to aggregate platelets with help of von Willebrand factor (vWF). It is used to diagnose von Willebrand disease (vWD).
Ristocetin aggregation test
105
An inherited deficiency in clotting factor VIII, which causes increased bleeding and usually affects males.
Hemophilia A
106
Inheritance of Hemophilia A
X-linked recessive trait, and thus occurs in males and in homozygous females
107
A blood clotting disorder caused by a mutation of the Factor IX gene, leading to a deficiency of Factor IX
Hemophilia B (the second most common form of hemophilia)
108
Inheritance of Hemophilia B
It is an X-linked recessive trait (The factor IX gene is located on the X chromosome). It can arise de novo without a family history
109
A pathological activation of coagulation (blood clotting) mechanisms that happens in response to a variety of diseases. It leads to the formation of small blood clots inside the blood vessels throughout the body. As the small clots consume coagulation proteins and platelets, normal coagulation is disrupted and abnormal bleeding occurs
Disseminated intravascular coagulation (DIC)
110
What effect does DIC have on organs in the body
The small clots disrupt normal blood flow to organs (such as the kidneys), which may malfunction as a result.
111
a zinc-containing metalloprotease enzyme that cleaves von Willebrand factor (vWf). It is secreted in blood and degrades large vWf multimers, decreasing their activity
ADAMTS 13
112
A disease characterized by hemolytic anemia (anemia caused by destruction of red blood cells), acute kidney failure (uremia), and a low platelet count (thrombocytopenia). It predominantly, but not exclusively, affects children. Most cases are preceded by an episode of infectious, sometimes bloody, diarrhea caused by E. coli O157:H7, which is acquired as a foodborne illness or from a contaminated water supply.
Hemolytic uremic syndrome (HUS)
113
The condition of having an abnormally low platelet count (thrombocytopenia) of unknown cause (idiopathic). Most incidents appear to be related to the production of antibodies against platelets.
Idiopathic/Immune thrombocytopenic purpura (ITP)
114
A rare disorder of the blood-coagulation system, causing extensive microscopic clots to form in the small blood vessels throughout the body. These small blood clots, can damage many organs including the kidneys, heart and brain. In the era before effective treatment with plasma exchange, the fatality rate was about 90%
Thrombotic thrombocytopenic purpura (TTP)
115
Diagnose: PT = high, PTT = high, bleeding time = high, platelets = low
Liver Failure or DIC
116
Diagnose: PT = high, PTT = normal or high, bleeding time = normal, platelets = normal
Vit K Deficiency
117
Diagnose: PT = normal, PTT = high, bleeding time = high, platelets = normal
VWF Disease
118
Diagnose: PT = normal, PTT = high, bleeding time = normal, platelets = normal
Hemophilia A & B
119
Presentation: Acute Idiopathic/Immune thrombocytopenic purpura (ITP)
Disorder of childhood with equal distribution between both sexes. Onset is abrupt and may be preceded by a viral illness. Usually resolves spontaneously within 6 months. May progress to chronic ITP in about 20% of cases.
120
Presentation: Chronic Idiopathic/Immune thrombocytopenic purpura (ITP)
More common than acute. Presentation: usually women \<40 with mucocutaneous bleeding, epistaxis, menorrhagia, and petechiae
121
IgGs against GPIIb-IIIa and GPIb-IX. Opsonized platelets destroyed by cells of mononuclear phagocyte system (spleen). Suppression of megakaryocyte proliferation and maturation, although these are usually present in approximately normal numbers. Cytotoxic T cells may also play a role. Generalized defect in immune regulation (too few regulatory T cells and B cells)
Chronic Idiopathic/Immune thrombocytopenic purpura (ITP)
122
Occurs in 5% of patients receiving heparin
Heparin-induced thrombocytopenia
123
Occurs rapidly after beginning heparin therapy and is clinically not significant.
Type I Heparin-induced thrombocytopenia
124
Occurs 5-14 days after beginning heparin therapy.
Type II - Heparin-Induced Thrombocytopenia/ Thrombosis Syndrome (HITTS).
125
Antibodies directed against complex of heparin and platelet factor 4 (PF4). Heparin binding exposes a neoepitope on PF4, which forms a tetramer on the platelet membrane. Immune complexes on the platelet surface cause platelet activation by binding the activating low affinity receptor for IgG
Type II - Heparin-Induced Thrombocytopenia/ Thrombosis Syndrome (HITTS).
126
Pentad of symptoms common to syndromes of thrombotic microangiopathies
Fever, thrombocytopenia, microangiopathic hemolytic anemia, transient neurologic deficits, and renal failure.
127
Usually presents in adults and neurologic symptoms are common. It usually occurs due to acquired antibodies to ADAMTS13 causing spontaneous aggregation of platelets by large VWF multimers. Can also be due to hereditary defect
Thrombotic thrombocytopenic purpura (TTP)
128
Usually presents in children. It may occur with an infectious gastroenteritis with bloody diarrhea. Renal symptoms dominate, but neurologic symptoms are less common. Caused by direct damage to endothelium due to E. coli O157:H7 toxin related to shiga toxin.
Hemolytic uremic syndrome (HUS)
129
Associated with inherited deficiency of inhibitors of the alternative complement pathway. Endothelial damage due to complement activation leads to microvascular thrombosis
Atypical Hemolytic uremic syndrome (HUS)
130
Direct infection of megakaryocytes by HIV. CD4 and CXCR4 receptors for HIV are present on megakaryocytes. Antibodies against HIV gp120 antibodies cross react with GPIIbIIIa cause secondary ITP
HIV associated thrombocytopenia
131
Most common blood component associated with bacterial contamination
Platelets
132
Administering what will cause von Willebrand factor to bind the platelet receptor glycoprotein Ib (GpIb)
The antibiotic ristocetin
133
What happens when ristocetin is added to normal blood
It causes agglutination
134
Where does Von Willebrand factor come from
The majority comes from the endothelial cell (Weibel–Palade bodies are the storage granules of endothelial cells. They store and release two principal molecules, von Willebrand factor and P-selectin.) but some comes from the platelet itself.
135
What is the role of ADP in hemostasis
ADP induces the expression of GpIIb/IIIa receptors on the surface of the platelet
136
What is the clinical presentation of a primary hemostasis problem
Mucosal (epistaxis, hemoptysis, GI bleeding, hematuria, and menorrhagia) and skin bleeding (petechia\*, purpura, ecchymoses, and easy bruising). Intracranial bleeding occurs with severe thrombocytopenia. \*Petechia are a sign of thrombocytopenia and are not usually seen with qualitative disorders
137
Name this disorder: Splenic plasma cell production of autoimmune IgG against platelet antigens (GpIIb/IIIa). Platelets bound by this autoimmune IgG get consumed by macrophages in the spleen
Immune thrombocytopenic Purpura (ITP)
138
What is the most common cause of thrombocytopenia in children and adults
Immune thrombocytopenic Purpura (ITP)
139
What is the clinical presentation of Acute Immune thrombocytopenic Purpura (ITP)
It occurs in children, weeks after a viral infection or immunization. It is self-limited, usually resolving within weeks of presentation. PT/PTT are normal. Platelet count is low (\<50k/ul), Increased megakaryocytes on bone marrow biopsy
140
What is the clinical presentation of Chronic Immune thrombocytopenic Purpura (ITP)
Usualy arises in women of child bearing age. It may be primary or secondary (SLE) and may cause short-lived thrombocytopenia in offspring (anti-platelet IgG can cross the placenta). PT/PTT are normal. Platelet count is low (\<50k/ul), Increased megakaryocytes on bone marrow biopsy
141
Why would splenectomy (only performed in refractory cases) be used to treat Immune thrombocytopenic Purpura (ITP)
It eliminates the primary source of antibody and the site of destruction
142
What is the cause of Thrombotic Thrombocytopenic Purpura (TTP)
Decreased ADAMSTS13 (autoantibody against it or genetic mutation in ADAMSTS13 gene) which normally cleaves multimers of Von Willebrand Factor for eventual degradation. Large uncleaved multimers lead to abnormal platelet adhesion, resulting in microthrombi
143
What are the clinical features of TTP and HUS
1. Skin and mucosal bleeding
2. Microangiopathic hemolytic anemia
3. Fever
4. Renal insufficiency
5. CNS abnormalities
144
What are the laboratory findings in TTP and HUS
1. Thrombocytopenia with increased bleeding time
2. Normal PT/PTT
3. Anemia with schistocytes
4. Increased megakaryocytes
145
What is Bernard-Soulier Syndrome
A genetic GpIb deficiency That causes impaired platelet _adhesion_. The blood smear shows mild thrombocytopenia with enlarged (more immature) platelets
146
What is Glanzmann Thrombasthenia
A genetic deficiency of GpIIb/IIIa causing impaired platelet _aggregation_
147
What effect does aspirin have on platelets
It irreversibly inactivates cyclooxygenase causing a lack of TXA2 impairing platelet _aggregation_
148
What effect does uremia have on platelet function
Uremia disrupts both platelet adhesion and aggregation
149
What is the clinical presentation of a secondary hemostasis problem
Deep tissue bleeding into muscles and joints and rebleeding after surgical procedures
150
What activates the intrinsic and extrinsic pathways of coagulation
Intrinsic (PTT) = Subendothelial Collagen
Extrinsic (PT) = Tissue Thromboplastin
151
What is the clinical presentation of Hemophilia A
1. Presents with deep tissue, joint, and post surgical bleeding (depending on severity of deficiency)
2. Elevated PTT (this will be corrected in a mixing study when normal plasma is added to patient plasma)
3. Normal PT
4. Decreased Factor 8
5. Normal platelet count and bleeding time
152
What is the clinical presentation of Hemophilia B
1. Presents with deep tissue, joint, and post surgical bleeding (depending on severity of deficiency)
2. Elevated PTT
3. Normal PT
4. Decreased Factor 9
5. Normal platelet count and bleeding time
153
How can you determine if there is a coagulation factor deficiency or an autoantibody to that coagulation factor
Mixing study: Add normal plasma to patient plasma. If it corrects the aberrant PT/PTT then it is a coagulation factor deficiency. No correction = autoantibody
154
What is the most common inherited coagulation factor disorder
Von Willebrand Disease (usually autosomal dominant mutation leading to decreased vWF levels)
155
What is the clinical presentation of Von Willebrand Disease
1. It presents with mild mucosal and skin bleeding
2. Increased bleeding time
3. Increased PTT (vWF stabilizes Factor 8) but not enough secondary hemostasis impairment to create symptoms
4. Normal PT
5. Abnormal ristocetin test (no aggregation of platelets with addition of ristocetin)
156
What is the treatment for Von Willebrand Disease
Desmopressin: Increases vWF release from Weibel-Palade bodies of endothelial cells
157
What effect does liver failure have on hemostasis
1. Decreased production of coagulation factors
2. Decreased activation of vitamin K by epoxide reductase (present in the liver)
3. Effect of liver failure is followed using PT
158
What does Heparin associate with on the surface of platelets to cause Heparin-induced Thrombocytopenia (HIT)
Platelet Factor 4 (antibodies form against the heparin-platelet factor 4 complex and destroys platelets. Fragments of destroyed platelets may activate remaining platelets - leading to thrombosis)
159
What are the laboratory findings in Disseminated Intravascular Coagulation (DIC)
1. Decreased Platelet count
2. Increased PT/PTT
3. Decreased fibrinogen
4. Microangiopathic hemolytic anemia
5. Elevated fibrin split products (D-Dimer)
160
What activates and inactivates plasmin
1. Tissue Plasminogen Activator (tPA) activates plasmin
2. Alpha2-antiplasmin inactivates plasmin
161
Overactive fibrinolysis presents like DIC but can be differentiated how, and how is it treated
1. Increased PT/PTT (plasmin destorys coagulation factors) - same as DIC
2. Increased bleeding time with normal platelet count (plasmin blocks platelet aggregation) - same as DIC
3. Increased fibrinogen split products **_without D-Dimers_** (serum fibrinogen is lysed, however, D-dimers are not formed because fibrin thrombi are absent)
4. Treated with aminocaproic acid - blocks the activation of plasminogen
162
What would you see in a pre-mortem thrombus that you would not see in a post-mortem thrombus
1. Lines of Zahn (alternating layers of blood cells and fibrin)
2. Attachment to vessel wall
163
What are the 3 major risk factors for thrombosis
1. Disruption of blood flow (stasis: immobilization, cardiac wall dysfunction , aneurysm)
2. Endothelial cell damage (atherosclerosis, vasculitis, high levels of homocysteine)
3. Hypercoagulable state
164
Besides the deep veins of the leg, where else does a DVT occur
Hepatic and cerebral veins
165
What do Protein C and Protein S do
1. Protein S is a cofactor for Protein C
2. Deficiency in Protein C and Protein S causes a hypercoagulable state
3. They decrease negative feedback on the coagulation cascade
4. They normally inactivate factors V and VIII
5. Increased risk for warfarin skin necrosis (warfarin inhibits Protein C and Protein S)
166
What is Factor V Leiden
1. Mutated form of Factor V that lacks cleavage site for deactivation by proteins C and S
2. Most common inherited cause of hypercoagulable state
167
What is Prothrombin 20210A
1. Inherited point mutation in prothrombin
2. Results in increased gene expression
3. Promotes thrombus formation
168
What is anti-Thrombin III deficiency
1. Decreases protective effect of heparin-like molecules produced by the endothelium, increasing the risk for thrombus
2. PTT does not rise with standard heparin dosing (because heparin works by activating anti-thrombin III, which is deficient)
3. High doses of heparin activate limited ATIII; coumadin is then given to maintain anticoagulated state
169
Why are oral contraceptives associated with a hypercoagulable state
1. Estrogen induces increased production of coagulation factors
2. Increases the risk of thrombosis
