Haematology Flashcards
1
Q
what happens in antithrombin deficiency?
A
decreased inhibition of factor IIa and Xa
2
Q
symptoms of DVT?
A
swelling, redness, warmth, pain
post-thrombotic syndrome (damage to valves)
3
Q
Absence of GpIb surface glycoprotein results in?
A
Bernard Soulier syndrome
( only 1 b in Gp1b and in Bernard soulier)
It is a Platelet adhesion problem
4
Q
clinical features of coagulation disorders?
A
- bleeding into deep tissues muscles and joints
2. bleeding delayed but prolonged
5
Q
what questions would you ask a patient whose labs suggest iron deficiency aneamia?
A
Menstrual/postmenopausal bleeding Diet - vegetarian/vegan GI symptoms - dysphagia/dyspepsia/abdominal pain/change in bowel habit/hematemesis/rectal bleeding/melaena Aspirin/NSAIDs Weight loss
6
Q
role of coagulation?
A
To generate thrombin (IIa), which will convert fibrinogen to fibrin
7
Q
Why is aspirin used as anti platelet therapy?
A
Decreases thromboxane A2. Decreases platelet activation
8
Q
what happens in factor V leiden?
A
Mutant factor 5. The coagulation factor is resistant to degradation by activated protein C
9
Q
functions of B12?
A
DNA synthesis, homocysteine metabolism
Integrity of the nervous system
10
Q
What is used to treat hemophilia A?
A
Desmopressin
11
Q
below which platelet count is spontaneous bleeding common?
AND severe spontaneous bleeding?
A
- <40 x 10^9
2. for severe spontaneous bleeding <10 x 10^9
12
Q
What is the effect of direct Xa inhibitors on PT and PTT?
A
Prolong both
13
Q
What is the result of absence of factor XI?
A
bleed after trauma but not spontaneous
14
Q
conditions associated with AIHA?
A
SLE - polyarthritis, renal impairment, facial skin rashes, hepatitis, tiredness
CLL
*positive dat test. Splenomegaly
15
Q
what do lab tests show in DIC?
A
increase in FDPs (D-dimers) - due to activation of fibrinolysis
decrease in fibrinogen
16
Q
what causes a prolonged PT and normal APTT
A
factor 7 deficiency
17
Q
mechanism of ITP
A
anti-GpIIb/IIIa antibodies bind to platelets -> destruction by splenic macrophages
- blood smear will show megakaryocytes but other cell counts will be fine
- May be associated with viral illness
- decrease in platelet count
18
Q
Give two possible investigations you would undertake if a disorder of primary heamostasis is suspected.
A
platelet count
vWF assay
clinical examination
19
Q
signs of B12 deficiency?
A
paresthesia
Pale Yellow tinge to skin
Changes in the way you move or walk around
Reversible dementia
20
Q
causes of vessel wall disorder?
A
- hereditary hemorrhagic telangiectasia, Ehlers-Danlos Syndrome
- Acquired - steroid therapy, aging (senile purpula), vasculitis, scurvy
Usually affect collagen synthesis
21
Q
causes of thrombocytopenia (low platelet count)?
A
- Bone marrow failure - leukemia, B12 deficiency
- Accelerated clearance - Immune (ITP) is common, Disseminated Intravascular Coagulation (DIC)
- Pooling and destruction in enlarged spleen (e.g cirrhosis and portal hypertension
22
Q
What is the result of absence of prothrombin (Factor II)?
A
lethal
23
Q
a patients VWF is found to show reduced platelet adhesion, what type of Von
Willebrand disease does this indicate?
A
type 2
24
Q
how does LMWH work?
A
enhances antithrombin- predominantly inactivates Xa
25
Direct Xa inhibitors decrease the formation of —
Thrombin
26
If a patient with iron deficiency anemia reports weight loss and intermittent abdominal pain, what investigations do you order?
1. FIT for blood in stool
2. Upper Gi endoscopy, duodenal biopsy, colonoscopy (GI investigations)
3. Coeliac antibody testing
27
causes of megaloblastic aneamia?
Vitamin B12 and folate deficiency
Agents or mutations that impair DNA synthesis:
azathioprine cytotoxic chemotherapy
Folate antagonists - methotrexate
Bone marrow cancers - myelodysplastic syndrome
28
what is DIC?
widespread activation of clotting factors leading to deficiency
platelets also consumed -> thrombocytopenia
29
what are common symptoms of anemia?
Fatigue, pallor, dyspnea, tachycardia
30
absence of GpIIb/IIIa surface glycoprotein results in?
Glanzmann's thrombasthenia
2 A’s, 3’s in Glanzmann’s = GpIIb/IIIa
It is a platelet aggregation problem
31
what are some causes of DIC?
1. sepsis
2. major tissue damage
3. inflammation
32
Patient with Rheumatoid Arthritis, low hb, slightly low MCV, reticulocytes on low end
Low serum iron. Low transferrin. High ferritin. Normal transferrin saturation. High ESR. blood film shows microcytic hypochromic rbcs. Elevated platelet count. What is the diagnosis?
aneamia of chronic disease
33
warfarin is a substrate for cytochrome p450
name some p450 inhibitors that would cause increased plasma levels of warfarin -> bleeding on warfarin
name some p450 inducers
inhibitors:
- fluconazole
- erithromycin/clarithromycin
- ciprofloxacin
- omeprazole
- some anti-HIV drugs, especially protease inhibitors
- grapefruit juice
inducers
- st. johns wort
- Rifampicin (anitbiotic used to treat TB)
- Antiepileptics - carbamazepine, phenytoin, phenobarbitone, primidone
- griseofulvin (antifungal)
34
treatment for hereditary spherocytosis?
Folic acid to help make new red blood cells
| Splenectomy if severe to increase rbc life span
35
other causes of normocytic aneamia?
Recent blood loss:
- Gastrointestinal haemorrhage, trauma
Failure of production of RBCs:
- Early stages of iron deficiency
- Bone marrow failure or suppression (e.g. chemotherapy)
- Bone marrow infiltration (e.g. leukaemia)
Pooling of RBCs in spleen:
Hypersplenism, e.g. liver cirrhosis
Splenic sequestration in sickle cell anaemia
36
state causes of Folic acid deficiency
1. diet - alcoholics, poverty
2. malabsorption - coeliac disease, jejunal resection
3. increased demand - hemolytic aneamia, pregnancy
treat with oral supplements
37
increase of which coagulant proteins can result in thrombosis?
1. prothrombin mutation/ Factor II
2. Factor 5 leiden
3. Factor 8 mutation
38
4 side effects of Warfarin?
1. bleeding
2. skin necrosis
3. purple toe syndrome
4. teratogenic - chondrodysplasia punctata
39
A patient with a disorder of primary haemostasis shows no evidence of petetchiae. What cause of the symptoms might this allow you to rule out?
thrombocytopenia
40
causes of macrocytic aneamia?
Lack of vitamin B12 or folic acid: megaloblastic anaemia
Use of drugs interfering with DNA synthesis
Liver disease and ethanol toxicity
Haemolytic anaemia (reticulocytes increased)
41
what is virchows triad?
SHE
1. stasis of blood flow - surgery, long haul flights, pregnancy
2. hypercoagulability - dominant in venous thrombosis
3. endothlial damage - dominant in arterial thrombosis
42
differentiate between purpura and petechiae
purpura dont blanch when pressure is applied
| pupura are larger
43
what deficiencies can result in thrombosis?
of anticoagulant proteins
1. antithrombin deficiency
2. protein C or S deficiency
44
State Important deactivators of coagulation. Deficiency Of them lead to what
1. Antithrombin lll
2. Protein C and protein S(cofactor)
3. Tissue factor pathway inhibitor
Hypercoagulation
45
what neurological disorders can present with B12 and folate deficiencies?
```
Folate = neural tube defect
B12 = Dementia and SACD
```
46
state 3 situations that require use of anticoagulants as prophylaxis
1. following surgery
2. during hospital admission
3. during pregnancy
47
findings in hereditary spherocytosis?
signs of hemolytic anemia
Spherocytes on blood film - small, spherical, no central pallor
Splenomegaly
48
Which type of heparin medication requires monitoring?
UFH - results in prolongation of APTT
49
What is the main function of Plasmin?
- Degrade clots to FdPs and D-dimers
50
signs and symptoms of iron deficiency aneamia?
Symptoms - fatigue, conjunctival pallor, pica, spoon nails
Labs show Low ferritin and serum iron. High transferrin/TIBC. Low transferrin saturation
Hb electrophoresis shows no increase in HbA2 (ruling out b- thalassemia)
Blood film shows small hypochromic cells
51
what happens in protein C or S deficiency?
decreased ability to inactivate Va and VIIIa
52
why does warfarin cause skin necrosis?
initial risk of hyper-coagulation when using the drug - protein C depletes initially before the other clotting factors get depleted. So blood clots form which block blood flow to skin
53
findings in G6PD deficiency
1. Labs consistent with hemolytic anemia
2. Blood film shows heinz bodies (precipitated oxidised haemoglobin) and bite cells
3. Ghost cells and hemighost cells from intravascular hemolysis
54
Effect of factor XII deficiency?
no bleeding.
doesn’t cause bleeding problems
But it causes prolonged PTT
This because Thrombin instead can activate other parts of the clotting cascade
55
spontaneous joint bleeding in hemophilia is called?
haemarthrosis
56
causes of iron deficiency aneamia?
```
Blood loss (most common cause in adults) due to :
Hookworm (most common worldwide)
menorrhagia
GI loss
Insufficient GI iron intake:
Dietary - vegetarians, vegan
Malabsorption - Coeliac disease, H. pylori gastritis
Increased iron requirements:
Pregnancy, infancy
```
57
findings in AIHA?
```
signs of hemolytic anemia
DAT test (adding anti-human globulin to patient RBC and antibody complex) = positive
```
58
name some triggers in a patient with G6PD deficiency
fava beans, oxidant drugs, napthalene, infection
59
What diagnostic tests can be used to determine B12 deficiency
Methylmalonic acid test - will be high
| Test for intrinsic factor antibodies - used to diagnose pernicious aneamia
60
functions of folate?
DNA synthesis, homocysteine metabolism
61
state 4 causes of resistance to warfarin
Diet - increased vitamin k intake
Lack of medication compliance
Increased metabolism from drug interactions
Reduced binding
62
what do you monitor when administering LMWH?
anti-xa activity
63
what are the clinical features in disorders of primary haemostasis?
1. superficial prolonged bleeding from cuts/ after trauma/surgery - immediate
2. mucosal bleeding (epistaxis, menorrhagia, gum bleeding)
3. ecchymosis
4. Petechiae - from thrombocytopenia
5. purpura - from platelet or vascular disorders
*severe VWD can result in haemophilia-like bleeding due to low FVIII
64
what anticoagulant do you use for atrial fibrillation?
DOACs or Warfarin
65
what anticoagulant do you use for a prosthetic heart valve?
Warfarin
66
which drug works by increasing anticoagulant activity?
heparin
67
functions of haemostasis?
1. prevent blood loss from injured vessels
2. arrest bleeding from injured vessels
3. enable tissue repair
68
When a patient presents with a normocytic nonhemolytic anemia, what is the next investigation you order?
iron studies - as condition may be caused by iron deficiency or aneamia of chronic disease or things that are not iron related
69
causes of increase in fibrinolytic factors
1. tPA
| 2. Heparin - potentiates antithrombin
70
functions of VWF?
1. Binding to collagen and capturing platelets
| 2. Stabilising factor VIII - may be low if VWF is low
71
how does aspirin work
irreversibly blocks COX enzyme
| inhibits the production of thromboxane A2 from arachidonic acid
72
Why is an elevated d-dimer used for DVT/PE diagnosis
Indicates clot breakdown
73
state some direct Xa inhibitors
rivaroXaban
| apiXaban
74
state 4 causes of prolonged APTT and PT
1. Liver disease
2. anticoagulant drugs
3. DIC
4. blood transfusion
5. vitamin K deficiency?
75
state some direct thrombin inhibitors
Digabatran
76
which drug/s work by lowering procoagulant factors
warfarin, DOACS
77
state 4 causes of prolonged APTT and normal PT
1. haemophilia A
2. haemophilia B
3. factor XII deficiency
4. factor XI deficiency
*PTT Is intrinsic pathway - play Table Tennis Inside
78
Low MCH, MCHC and MCV are found in what type of anemia?
Microcytic hypochromic anemia
79
_ FDPs and d-dimers and _ fibrinogen are hallmarks of DIC
High
| Low
80
what is the normal range for platelet count
150 x10^9 - 400 x10^9
81
describe some novel treatments for haemophilia
1. gene therapy
2. bispecific antibodies in Haemphilia A
3. RNA silencing - targets antithrombin
82
symptoms of pulmonary embolism
Tachycardia (palpitations), hypoxia, shortness of breath
Chest pain, hemoptysis,
Sudden death
83
causes of bleeding?
1. reduction in coagulation factors and platelets (failure of production or increased consumption vs defective function)
2. increase in fibrinolytic factors and anticoagulant proteins
84
how do DOACs work?
Factor Xa (direct Xa inhibitors) or IIa (direct thrombin inhibitors).
85
what is warfarins mechanism of action?
Warfarin inhibits vitamin K epoxide reductase
| thus preventing the vitamin K-dependent carboxylation of factor II, VII, I, Protein C, Protein S
86
storage pool disease results in?
reduction in granular content of dense granules of platelets - ADP, calcium, serotonin
87
how do you monitor warfarin administration?
using INR = PT/PTc. normal = 1
| target with warfarin = 2-3
88
what is chondrodysplasia punctata?
early fusion of epiphyses
89
which clotting factor does warfarin reduce most quickly
VII
90
A 35 year old woman presents suffering regular prolonged nosebleeds and has noticed she bruises
easily when playing sport. She also notes that her menstrual bleeding has been heavier than usual in
recent months.
What phase of haemostasis is likely to be disrupted in this patient?
primary
91
causes of extrinsic hemolytic aneamia?
1. Immune mediated - AIHA, Allo immune/post blood transfusion
2. None immune- Microangiopathic (HUS leads to this), macroangiopathic, infections. snake venom, drugs.
92
describe the pathophysiology of aneamia of chronic disease
1. IL-6 released during inflammation. This Increases hepcidin levels which blocks iron absorption and release by binding to ferroportin on intestinal mucosal cells and macrophages
2. Decrease EPO production
93
what are the classic findings in hemolytic aneamia?
1. normocytic aneamia
2. ↑reticulocyte count
3. ↑ LDH
4. ↑ unconjugated bilirubin
5. ↓ haptoglobin (lower in intravascular)
6. Urine Hb and hemosiderin (intravascular)
94
how does UFH work?
Enhances antithrombin - helps bind and inactivate Factor Xa and thrombin
IV drug
95
what are the 3 main causes of coagulation disorders
1. Deficiency of coagulation factor production
2. Dilution - blood transfusions (red cell transfusions do not contain plasma. Must replace plasma in major hemorrhage as well as red cells and platelets)
3. Increased consumption - DIC, autoimmune (production of coagulation factor inhibitors)
96
consequence of DIC?
fibrin deposition in vessels can cause organ failure
97
Direct thrombin inhibitors decrease formation of___
Fibrin
98
state causes of B12 deficiency and how to treat it
1. diet
treat with supplements
2. gastric/intrinsic factor - pernicious aneamia and gastrectomy
treat with hydroxocobalamin injections
3. terminal ileum - chron's disease, ileal resection
treat with the injections
99
name 3 conditions that require a therapeutic use of anticoagulants?
1. venous thrombosis
2. atrial fibrillation
3. mechanic prosthetic heart valve
100
causes of impaired function of platelet?
1. Glanzmann's thrombasthenia
2. Bernard Soulier Syndrome
3. Storage pool disease
4. Aspirin, NSAIDs, Clopidogrel
101
A patient is on warfarin. Why might malnutrition result in an increase in their INR?
Metabolism of some drugs affected by malnutrition
Malnutrition decreases plasma protein levels (warfarin is heavily plasma protein bound):
- Decreases oxidative metabolism
- Decreased GFR
102
What is INR? What does a fall in INR signify?
International normalised ratio - Standardised measure of blood clotting time
PT patient/PTnormal
Fall in INR = Increased clotting, decreased bleeding
If INR falls below 2.0 thrombosis risk increases for a patient predisposed to clotting
103
how does clopidogrel work?
inhibits ADP from binding to its P2Y12 receptor on platelet)
104
state some common causes of anaemia of chronic disease
chronic infections(TB, HIV), autoimmune disorders like RA, malignancy
105
causes of von willebrand disease?
How does it manifest?
1. Hereditary decrease of quantity (Type 1 or 3) or function of the factor (Type 2)
2. May be acquired due to antibody
- NORMAL Platelet count and PT. PTT may or may not be elevated due to factor 8 deficiency
106
what tests are carried out for coagulation disorders
1. clotting screen - APTT, PT, platelets
2. assays for factor 8
3. test for inhibitors
107
5 causes of deficiency of coagulation factor production?
1. factor 8 deficiency - hemophilia A
2. factor 9 deficiency - hemophilia B
3. liver disease
4. anticoagulant drugs - warfarin, DOACs
5. vitamin k deficiency
108
what is purple toe syndrome?
disrupted atheromatous plaques bleed
| cholesterol emboli lodge in extremeties
109
which anticoagulant has some renal dependence?
DOACs
110
A Patient with hemolytic anaemia later presents with upper right abdominal pain, more marked jaundice and higher bilirubin which is mainly conjugated. What is the cause?
pigment Gallstones from increased breakdown of hb to bilirubin
Has obstructed common bile duct - buildup of conjugated bilirubin that cant pass to duodenum
111
how do you slowly and rapidly reverse warfarin action?
Slowly - vitamin k administration
| Rapidly - infusion of coagulation factors- PCC or FFP
112
when do you use FFP?
to replace all coagulation factors
113
what lab tests are carried out for disorders of primary haemostasis.
1. platelet count - normal or low depending on condition
2. bleeding time - prolonged
3. assays of von Willebrand factor
4. coagulation screen - NORMAL except in mixed disorders. PT and APTT prolonged in DIC. PTT may be prolonged in severe cases of VWD
*primary, think PLATELET problem
114
what anticoagulant do you use in pregnancy?
LMWH (DOACs not safe)
115
how do you treat abnormal primary haemostasis?
1. failure of production - replace missing factors or platelets. stop aspirin/NSAIDs
2. immune destruction - steroids(prednisolone) or splenectomy for refractory ITP
3. increased consumption - replacement and treatment of cause
4. VWD - desmopressin to release vWF
5. tranexamic acid (anti-fibrinolytic), fibrin glue, OCP for menorrhagia
116
when do you use cyroprecipitate?
coagulation factor deficiencies of fibrinogen and factor 8
117
how do you treat coagulation disorders?
1. factor replacement:
- factor concentrates
- FFP
- cyroprecipitate
2. desmopressin, tranexamic acid, fibrin glue, OCP
118
findings in megaloblastic aneamia?
Hypersegmented neutrophils, RBC macrocytosis elevated MCV
119
What protein transports iron in the blood?
Transferrin
120
What protein stores iron? Where?
Ferritin
| In macrophages of liver and bone
121
What happens to transferrin when iron stores are low?
Transferrin levels rise
122
What key molecule causes anaemia of chronic disease?
Hepcidin
| It binds ferroportin in enterocytes and macrophages
123
What are the iron studies in anaemia of chronic disease?
Increased ferritin - iron trapped in storage form
Decreased serum iron
Decreased transferrin
124
How would you treat anaemia of chronic disease?
Ibuprofen
125
In a patient with SLE, state one way of differentiating between AIHA and Anemia of chronic disease being the cause of anaemia
AIHA will have a high reticulocyte count (hemolytic)
| And will also be normocytic
126
Spherocytes have _ MCHC
Elevated
