Flashcards in Hematology Deck (192):
1
Factors in extrinsic pathway
TF, VII
2
Factors in intrinsic pathway
VIII, IX, XI, XII
3
Sxs of platelet disorders
Bleeding from skin, mucous membranes, petechiae, small superficial ecchymoses.
Immediate bleeding after sx
4
Sxs coagulation disorders
Bleeding into soft tissues, joints, and muscles. Large deep ecchymoses. Delayed bleeding after sx.
5
Platelet disorders resulting from increased consumption
Immune: ITP, drugs
Non-immune: TTp-HUS, DIC
6
Platelet disorders resulting from decreased platelet fn
Inherited: gp Ib mutation; gpIIb/IIIa mutation; storage pool disease
Acquired: Aspirin, uremia
7
Type I VWD
AD. Partial VWF deficiency
8
Type II VWD
AD. Loss multimers-altered quality
9
Type III VWD
AR. Complete deficiency VWF
10
Presentation VWD
Decreased platelet adhesion-->presents as platelet problem.
Increased bleeding time, normal PT, aPTT
11
Tx-VWD
Desmopressin, VIII, VWF concentrates
12
Clotting derangements in Vit K defic
Increased PT and aPTT
13
Clotting derangements in liver disease
Increased PT, aPTT
14
Protein C or S deficiency
AD. Early thrombosis (<40 years)
15
Prothrombin mutation
Increases transcription, therefore more likely to clot
16
Factor V Lieden
Cannot be degraded by protein C
-> Thrombophilia
17
Causes of acquired thrombophilia
Immobility/stasis, tissue trauma (sx), malig, anti-phospholipid syndrome, high estrogen states
18
Classic signs anemia
Sxs hypoxia
Conjunctival pallor, koilonychia, glossitis, angular stomatits, post-cricoid webs, high flow murmur
19
Causes of cellular bone marrow infiltration
Myeloproliferation, myelofibrosis, malignant spread
20
Causes of hypocellular bone marrow infiltration
Idiopathic, cytotoxic drugs +radiation, infxns, AI
21
Elliptocytosis
AD. Mild. No tx
22
ALL presentation
Bone marrow failure, LAD, HSM, testicular infiltration
23
AML presentation
Bone marrow failure, bleeding tendency, GUM/skin/CNS infxns
24
CLL
Mostly B cell
Elderly
Indolent course with good prognosis
Increased lymphocytes
Smudge cells
25
Polycythemia rubra vera-presentation and defect
Elderly
Non-specific sxs: tired, depressed, vertigo, visual disturbances, HTN, angina, intermittent claudication
JAK2 mutation
26
Polycythemia rubra vera-tx
Venesection, hydroxyurea, radioactive 32P
27
Essential thrombocythemia
Benign hx
Decreased quality platelets so actually bleed
Hypercellular marrow
JAK2 mutation
Tx w/ hydroxyurea
28
MGUS
Elderly
Paraprotein present
29
AIP
Psychosis, seizures, abdo pain, polyneuropathy, port wine urine.
AD. Precipitated by stress.
Tx-analgesia, CHO
30
Bacterial infxn transfusion rxn
-Sxs
-Tx
Sxs: Sudden onset fever, v unwell.
Tx: Stop transfusion, broad spectrum abx
31
Viral infxns possible from blood transfusions
Hep B/C, HIV, CMV, HTLV
32
Graft v host disease-sxs
Skin rashes, organ failure, marrow failure, diarrhea
33
Acanthocytosis
Abetalipoproteinemia, liver disease, hyposplenism
34
basophilic stippling
Lead poisoning
Megaloblastic anemia
Myelodysplasia
Liver disease
Hemoglobinopathy
35
Burr cells (echinocytes)
Uremia, GI bleeidng, stomach carcinoma
36
Heinz bodies
G6PD def, chronic liver disease
37
Leukoerythroblastic anemia
Marrow infiltration, i.e. myelofibrosis, malignancy
38
Pelger Huet cells
Hyposegmented neutrophils
39
Polychromasia
Sign of reticulocytes: premature release from BM
40
Right shift
Megaloblastic anemia, uremia, liver disease
41
Rouleaux formation
Chronic inflamm, paraproteinemia, MYELOMA
42
Schistocytes
MIHA e.g. DIC, HUS, TTP, pre-eclampsia
43
Stomatocytes
"Smiling faces" or "fish mouth" RBCs
Hereditary stomatocytosis, high alcohol intake, liver disease
44
Target cells
"HALT"
HbC disease
Asplenia
Liver disease
Thalassemia
45
Hb components
Heme + globin
46
Heme components
Fe + protoporphyrin
47
Microcytosis
MCV
48
Normocytic anemia
MCV 80-100
ACUTE blood loss--first stage IDA
Bone marrow failure
Renal failure
Hypothyroidism
Hemolysis
Pregnancy
F
49
Macrocytic anemia
MCV>100
Alcohol excess
Liver disease
B12 defic, folate defic
Hypothyroidism (can also be normocytic)
50
Anisocytosis
Blood cells of varying size
51
Plummer Vinson syndrome
Anemia
Dysphagia (esoph webs)
Beefy red tongue
52
Common causes IDA
Menorrhagia
Peptic ulcers/gastritis
Polyps/CRC
Meckel's
Hookworm infestation
Dietary deficiency
Malabsorption
53
ACD
Fe sequestered by hepcidin in macrophage
Increased ferritin, decreased TIBC
Decreased Fe, decreased % saturation
Causes:
-Chronic infection (TB, osteomyelitis)
-Vasculitis
-RA
-Malignancy
54
Sideroblastic anemia
Iron loading causing hemosiderosis
Same lab findings as hemochromatosis
Causes: Pb poisoning, B6 deficiency (ALAS cofactor), ALAS defect, myeloprolif or myelodysplastic syndromes
55
In which two causes of anemia is Fe low?
IDA, ACD
56
TIBC and ferritin relationship
Oppose each other, i.e. if TIBC high then ferritin low
57
Ferritin
Only low in IDA
Acute phase protein; increases with inflamm e.g. infection, malignancy
58
Megaloblastic blood film
Hypersegmented (>5) neutrophils, leukopenia, macrocytosis, anemia, thrombocytopenia
59
B12 deficiency
Takes years to develop (large liver stores)
Diet: Strict vegans, boozers
Malabsorption: pernicious anemia, gastrectomy, probs with termina ileum (Crohns, bacterial overgrowth, tropical sprue, diphyllobothrium latum)
Pancreatic insufficiency
60
Lab findings ih hemolytic anemias
Increased: unconj bili, urobilinogen, LDH, reticulocytosis/RDW
Intravascular types have decreased haptoglobin
61
RBC membrane defect disorders resulting in hemolysis
Hereditary spherocytosis
Hereditary elliptocytosis
62
RBC enzyme defect conditions resulting in hemolytic anemias
G6PD def
PK def
63
Non-immune causes hemolytic anemias
Mechanical heart valves
PNH, MAHA
Infections (malaria)
Drugs
64
Hereditary spherocytosis
AD
Spectrin, ankyrin, band 3 defect
Osmotic fragility test
Parvo B19 susceptibility
Pigmented gallstones
Splenomegaly
Tx: splenectomy. Howell-Jolly bodies post-splenectomy
65
Hereditary elliptocytosis
AD
Spectrin or band 4.1 mutations
66
G6PD deficiency
X linked
African, Mediterranean, Middle Eastern
No G6PD=no NADPH (HMP shunt)=reduced glutathione=oxidative injury by H2O2=intravasc hemolysis
Oxidants (drugs-malaria drugs, sulfonamides, aspirin; fava beans; stress) cause rapid anemia and jaundice
Bite cells and Heinz bodies
Enzyme assay 2-3 months after attack
Intarvasc hemolysis: dark urine
67
Pyruvate kinase deficiency
AR
Severe neonatal jaundice, splenomegaly, hemolytic anemia
68
Sickle cell
AR
Glu ->valine position 6 of beta chain
Trait usu asymptomatic (except kidneys)
Manifests around 6mo (HbF as newborn)
Decreased O2 tension causes polymerization and sickling
Get vaso-occlusion and infarction: dactylitis, stroke, acute chest syndrome, renal papillary necrosis
Tx: analgesia, hydration, SHiN vaccines, hydroxyurea
69
Beta thal minor
Asymptomatic carrier, mild anemia
70
Beta thal intermedia
Moderate anemia, splenomegaly, bony deformity, gallstones
71
Beta thal major
Severe anemia, FTT, HSM (extramedullary hematopoiesis), bony deformity.
May have heart failure
72
2 alpha gene deletion
Alpha thal trait
Asymptomatic, mild anemia
73
3 alpha gene deletion
HbH disease
Moderate anemia, splenomegaly
74
4 alpha gene deletion
Hb Barts
Incompatible with life
75
Warm Agglutinin Autoimmune Hemolytic Anemia
IgG
Coombs positive
Cause: mainly idiopathic, may be lymphoma, CLL, SLE, methydopa
Tx: steroids, splenectomy, immunosuppression
76
Cold Agglutinin-Autoimmune Hemolytic Anemia
IgM
Positive Coombs test
Oft has Raynauds
Causes: primarily idiopathic. may be lymphoma, infections (EBV, mycoplasma pneumoniae)
Tx: treat underlying condition, avoid cold, chlorambucil
77
Paroxysmal cold hemoglobinuria
Hb-uria after viral infection (e.g. measles)
Donath-Landsteiner abs attach to RBCs in cold; complement-mediated hemolysis on rewarming
78
Paroxysmal Nocturnal Hemoglobinuria
Acquired loss GPI on RBC
GPI anchors DAF which protects against complement in blood. If you lose GPI, you lose DAF, therefore complement-mediated lysis
Dx: Hamm's test or immunophenotype showing altered GPI
79
Where in gut is iron absorbed?
Duodenum
80
Transferrin
Transports iron in blood.
81
Ferritin
Binds iron in storage
Note that Fe on its own causes ROS damage via Fenton reaction
82
TIBC
Measure of transferrin molecules in blood
83
% saturation
Percentage of transferrin molecules that are bound by Fe (normal is 33%)
84
Most common type of anemia in hospitalized patients
ACD
85
Hepcidin
Sequesters Fe in storage sites by:
1. Limiting transfer of Fe from macros to erythroid precursors
2. Suppressing EPO
86
lab findings in ACD
Increased ferritin, decreased TIBC
Decreased serum Fe and % saturation
Increased FEP
87
Lab findings in IDA
Decreased ferritin, increased TIBC
Decreased serum iron, decreased % saturation
Increased FEP
88
HbF
a2g2
89
HbA
a2b2
90
HbA2
a2delta2
91
Causes macrocytic anemia without megaloblastic change
Booze
Liver disease
Drugs (e.g. 5-FU)
92
Where is folate absorbed?
Jejunum
93
Difference in labs between folate and B12 deficiency
Folate: normal methylmalonic acid
B12: increased methylmalonic acid
Both have high homocysteine (increases risk thrombosis)
94
Corrected retic count
(Retic count falsely elevated in anemia, as normal RBCs gone so retics are overall higher percentage)
Retic count * Hct/45
95
Extravascular hemolysis
Destruction by reticuloendothelial system (macros of spleen, liver, LNs)
Findings:
Anemia, splenomegaly, unconj jaundice, risk bili gallstones
Marrow hyperplasia if corrected retic count >3%
96
Intravascular hemolysis
Hb-emia
Hb-uria
Hemosiderinuria (renal tubular cells pick up Hb and break down to Fe, accumulates and shed with tubular cells)
Decreased haptoglobin
97
Microangiopathic hemolytic anemia (MIHA)
Intravasc hemolysis from VASCULAR cause...RBCs destroyed as pass through circulation.
Caused by microthrombi (TTP-HUS, HIC, HELLP), prosthetic heart valves, aortic stenosis
Schistocytes
98
Fever patterns:
-Falciparum
-Vivax
-Ovale
-malariae
Falcip: every day
Vivax, ovale: tertian (every other day)
Malariae: quartan (every third day)
99
Aplastic anemia
Damage to hematopoietic stem cells (CD34+) cauing pancytopenia with low retic count
Causes: drugs/chemicals, viral infections, AI damage
Biopsy: empty, fatty marrow
100
Primary hemostasis
Formation of platelet plug
101
Secondary hemostasis
Stabilization platelet plug
Coag cascade mediated
102
Mucosal bleeding
Epistaxis (most comm), hemoptysis, GI bleeding, hematuria, menorrhagia
Symptom of platelet abnormality
103
Petechiae vs purpura vs ecchymoses
Petechia: 1-2mm
Purpura: >3mm
Ecchymoses: >1cm
NB petechiae are a sign of thrombocytopenia, not usu seen with qualitative platelet defects (just quantitative)
104
ITP
AI production IgG against platelet antigens, e.g. GpIIb/IIIa
MCC thrombocytopenia in adults
Ab-bound platelets consumed by splenic macros causing thrombocytopenia
Acute: post viral infection or immunization. Kids. Self-limiting
Chronic: primary or secondary. Women of child bearing age
105
TTP-HUS
TTP: ADAMTS13 deficiency
HUS: E. coli O157:H7 verotoxin destroys endothelial cells resulting in platelet microthrombi
"FATRN"
Fever
Anemia (MIHA)
Thrombocytopenia
Renal failure
Neuro sxs
106
Bernard-Soulier
GpIb deficiency--impaired platelet adhesion
Mild thrombocytopenia with enlarged platelets
107
Glanzmann thrombasthenia
GpIIb/IIIa deficiency--impaired platelet aggregation
108
Uremia's effect on platelets
Disrupts adhesion and aggregation of platelets
109
Clinical difference between hemophilia A and B
There is none, you numpty
110
Vitamin K deficiency--causes
Newborn (lack GI colonization)
Long term antibiotic therapy
Malabsorption of fat-soluble vitamins
111
Heparin-Induced Thrombocytopenia
Platelet destruction.
Fragments destroyed platelets may activate others, causing thrombosis
112
DIC
Widespread microthrombi result in ischemia and infarction
Consumption factors and platelets result in bleeding, esp from IV sites and mucosal surfaces
Causes:
Obstetric complications--tissue thromboplastin in amniotic fluid activates coag
Sepsis, esp E. coli and N men
Adenocarcinoma (mucin activates coag)
APML
Rattlesnake bites
113
Lab findings in DIC
Decreased: platelets, fibrinogen, D-dimer
Increased: PT, PTT
114
tPA
Converts plasminogen to plasmin
115
Plasmin
Cleaves fibrin and serum fibrinogen, destroys coag factors, blocks platelet activation
116
How do you distinguish thrombosis from postmortem clot?
Lines of Zahn
Attachment to vessel wall
(Both these found in thrombosis)
117
Mechanisms by which intact endothelium prevents thrombosis
Block exposure subendothelial collagen and underlying tissue factor
Produce PGI2 and NO (vasodilation and inhibition platelet agg)
Secrete heparin-like molecules
Secrete tPA
Secrete thrombomodulin
118
Causes endothelial cell damage :(
Atherosclerosis
Vasculitis
High levels homocysteine
119
Cystathionine beta synthase deficiency
Results in high levels homocysteine and homocystinuria.
Findings: vessel thrombosis, mental retardation, lens dislocation, long slender fingers
120
Protein C or S deficiency
AD
Increased risk warfarin skin necrosis
121
Most common cause inherited hypercoagulable state
Factor V Lieden
122
Prothrombin mutation
Point mutation in thrombin that causes increased gene expresion, therefore more thrombi (pro-thrombin...)
123
ATIII deficiency
Decreases protective effect of heparin-like molecules produced by endothelium
124
Why does estrogen (e.g. OCP) cause increased thrombosis risk?
Increased production coag factors
125
Types of emboli
Thrombo-embolism (MCC)
Fat embolism
Gas embolism
Amniotic fluid embolism
126
Fat embolus
BONE FRACTURES, esp long bones, and soft tissue trauma
Dyspnea and petechiae on skin over chest
127
Gas embolus
Decompression sickness--rapid ascent while diving
Nitrogen gas precipitates out during rapid ascent
Joint and muscle pains (the bends) and resp sxs (the chokes)
Chronic form=Caisson disease. Multifocal ischemic necrosis of bone
May also occur during laparoscopic surgery
128
Amniotic fluid embolism
Amniotic fluid enters maternal circulation during labor/delivery
SOB, neuro sxs, DIC
Squamous cell and keratin debris from fetal skin found in thrombus
Extremely high mortality: only 10% survive
129
Pulmonary embolism
Most often clinically silent due to dual blood supply of lung
Usually small and self-resolves
10% cause infarction: SOB, hemoptysis, pleuritic CP, pleural effusion
Sudden death if saddle embolus
Pulm HTN if chronic emboli that are reorganized over time
130
Systemic embolism
Usu due to thromboembolus
Most commonly arise in L heart
131
factor II
Aka thrombin
132
JAK 2
Non-receptor tyrosine kinase
Mutations found in:
PV
ET
Myelofibrosis
Other Myeloproliferative disorders
133
Acquired causes sideroblastic anemia
Alcoholism, Pb poisoning, B6 deficiency
134
Disorders with increased MCHC
Hereditary spherocytosis
AI anemia
135
Metabisulfite test
Detects both sickle cell and sickle cell trait, i.e. any presence of HbS
136
HbC disse
LYSINE instead glutamic acid HbC crystals
137
PNH-cause
ACQUIRED deficiency GPI
138
GPI
Anchors DAF and MIRL which degrade complement getting too close to RBCs
139
Test for PNH
Look for presence CD55 (aka DAF) on cells. If no CD55, then can assume no GPI
140
MCC death in PNH
Thrombosis, e.g. portal vein
10% go on to develop AML
141
HIT
Heparin destroys platelets. Some of destroyed platelets go on to activate other platelets causing THROMBOSIS
Do not use warfarin--increased incidence skin necrosis
142
Secondary causes DIC
Obstetric complications (amniotic fluid activates tissue thromboplastin), sepsis, adenocarcinoma, APML (Auer rods), rattlesnake bite
143
GpIb-function
Binds vWF
144
GpIIb/IIIa
Platelet AGGREGATION. Uses fibrinogen as linker
145
Petechiae are a sign of what problem?
QUANTITATIVE platelet problem, i. thrombocytopenia. Not seen in qualitative disorders
146
ITP
AI: IgG against platelet antigens (eg. GpIIb/IIIa).
Most common cause thrombocytopenia in kids and adults
Ab-bound platelets consumed by splenic macrophages
Spleen also one making antibody
Acute-kids. Usu post-viral infxn or immunization
Chronic-adult women (may be secondary to SLE)
Tx: steroids (esp if acute), IVIG, splenectomy
147
MIHA
Pathological formation microthrombi in small vessels, which shears RBCs. Use up platelets making microthrombi
TTP-HUS is a major cause
148
TTP-mechanism
Deficiency ADAMTS13--can't degrade vWF multimers. Pile up vWF multimers causes abn platelet adhesion thus microthrombi
149
HUS-mechanism
E. coli O157:H7 vertotoxin damages endotherlial cells causing platelet microthrombi. Also decreases ADAMTS13
Kids + undercooked beef -->dysentery
150
Signs and sxs TTP-HUS
Fever
MIHA
Thrombocytopenia
Renal insufficiency (esp HUS)
CNS abnormalities (esp TTP)
Increased bleeding time, normal PT/PTTtX-ttp-hus
151
Tx-TTP-HUS
Plasmapheresis, 'roids
152
Bernard-Soulier
Genetic gpIb deficiency
Impaired platelet adhesion
Mild thrombocytopenia with enlarged platelets ("Big Suckers")
153
Glanzmann's thrombasthenia
Deficienct gpIIb/IIIa
Impaired platelet aggregation
154
Indications for transfusion
Acute blood loss >30% blood volume
Peri-op/critical care, when Hb
155
Intra operative cell salvage
Collect blood lost during surgery and reinfuse into pt.
NB-washed/filtered so lose coagulation factors and platelets
156
Type of blood used in transfusions for highly immunosuppressed individuals
Irradiated
157
Reaction when use the wrong blood in transfusion
Signs/sxs Intravascular hemolysis
Restless, chest/loin pain, fever, vomiting, flushing, collapse, later--hemoglobinuria
158
Febrile non-hemolytic transfusion reaction
Increase in temp by 1 degree C, chills, rigors
Common before blood leukodepleted, now rare
Stop/slow transfusion, give paracetamol. Can re-start
159
Allergic transfusion reaction
Usually with plasma
Common
Mild urticarial or itchy rash +/- wheeze
Tx with antihistamines
160
Delayed hemolytic transfusion reaction
1-3% pts who have received transfusion
Develop Sb to one of foreign RBC antigens
Complement-mediated phagocytosis
Extravascular hemolysis
161
Anaphylactic reaction to blood transfusion
Hypotensive shock, very breathless, wheeze, laryngeal and facial edema
E.g. Donor eaten peanuts (antigen) and pt has IgE Ab to this antigen already
162
TACO
Transfusion Associated Circulatory Overload
Within 6 hrs
Acute resp distress, tachycardia, increased BP, acute or worsening pulm edema, positive fluid balance
163
TRALI
Transfusion Related Acute Lung INjury
Dry cough, dyspnea, fever, not due to fluid overload or other causes
Donor anti-leukocytic Abs interact with pt's leukocyte antigens causing aggregation. These aggregations get stuck in pulm caps. Neutrophils in aggregates release proteolytic enzymes that cause lung damage
Can prevent by giving virally-activated plasma, and plasma from men
164
Cabot rings
Looped structures in RBCs. Found in megaloblastic anemia
165
Pappenheimer bodies
Iron granules. Foud in sideroblastic anemia, Pb poisoning, hemolytic anemias
166
Prothrombin 20210A mutation
Substitution G to A at position 20210 of prothrombin gene. Increases transcription thus more clotting after vessel damage
5% Caucasian population
167
Post-transfusion purpura
5-9 days after transfusion
Severe thrombocytopenia with bleeding
Tx with IVIG
168
Pencil bodies
Type of elliptocyte
Seen in IDA, thal, PK deficiency
169
Cooley's anemia
Old name for beta thal major
170
Cabot rings
Looped structures in RBCs
Caused by megaloblastic anemia
171
Pappenheimer bodies
Iron granules. Pb poisoning, sideroblastic anemia, hemolytic anemia
172
Buerger's disease
Aka thromboangitis obliterans
Strong relation to smoking
Recurrent arterial and venous thromboses
Corkscrew arteries in upper and lower limbs
173
Protein S
Degrades Factors Va, VIIIa
174
Antithrombin
Inhibits thrombin, factor Xa
175
C-myc
Burkitts
176
Lymphoma with centrocytes, centroblasts
Follicular
177
Bcl-2 associated lymphoma
Follicular
178
Donath-Landsteiner Abs
Paroxysmal cold Hb-uria
179
Non-megaloblastic causes of macrocytic anemia
"RALPH"
Reticulocytosis
Alcohol
Liver disease
Pregnancy?
Hypothyroidism
180
Hemochromatosis-sxs
Hepatomegaly/deranged LFTs
Arthralgia and chondrocalcinosis
Diabetes
DCM
Hypogonadism/impotence
Adrenal insufficiency
Skin color changes (slate grey or bronze)
181
MM-lab findings
Normal ALP
Increased ESP
Increased Ca
182
MGUS
183
Waldenstroms
High IgM
Hyperviscosity and vascular complications
184
Combined polycythemia
Aka "smoker's polycythemia"
Combination decreased plasma volume and decreased O2 (CO displaces) causing an increase in EPO
Be very suspicious if smoker + COPD picture
185
Secondary polycythemia
Increase in EPO or testosterone (anabolic roids)
Ectopic EPO from HCC, RCC, hemangioblastoma, pheo, uterine myomata
186
Primary polycythemia
LOW EPO
E.g. polycythemia vera
187
Non-classical subtype of Hodgkins
Nodular lymphocytic
188
Ann Arbor Staging for Hodgkins
I: Single LN region
II: 2+ LN on SAME SIDE of diaphragm
III: LN on both sides diaphragm
IV: extranodal spread
Add "a" if no B sxs, add "B" if there are B sxs
189
B sxs
Significant unexplained fever
Night sweats
Weight loss >10% in preceding 6/12
190
Imantinib
Tyrosine kinase inhibitor.
Used in CML
191
Absence LONG arm chromo 5
Subtype of myelodysplastic syndrome
192