Anemias and Coagulation Flashcards
Where does the common coagulation cascade begin?
Factor X activation
What does PT measure?
Extrinsic + common pathway
What does PTT measure?
Intrinsic + common pathway
Where does the intrinsic pathway begin?
Factor XII
Where does the extrinsic pathway begin?
Factor VII activation by tissular factor
Heparin function in coagulation
Inhibit Xa
Primary hemostasis disorders are caused by _______ dysfunction
Platelet
Secondary hemostasis disorders are caused by ________ dysfunction
Coagulation
Primary hemostasis disorders manifestations
Mucous membrane bleeding
- Epistaxis
- Bleeding gums
- GI bleeding
Cutaneous:
- Petechiae
- Purpura
- Ecchymoses
- Easy bruising
- Menorrhagia
- Prolonged bleeding, but it STOPS
Secondary hemostasis disorders manifestations
Deep tissue bleeding
- Hemarthrosis
- Hematomas
Large, palpable ecchymoses
>80% male
Splenomegaly’s effect on platelets
Platelet sequestration of 90%
Mechanisms of failure of platelet production
Selective megakaryocytic depletion by drug or virus
Bone marrow failure
Mechanisms of increased platelet consumption (6)
- ITP
- TTP
- UHS
- Infections (HIV, protozoa, H.pylori, malaria)
- Post-transfusion (10 days)
- Drug-induced (heparin)
Glanzmann’s disease
Primary aggregation of platelet failure because of IIb/IIIA deficiency
Bernard-Soulier sx
Large platelets without GPIb and defective adhesion
Half-life of platelets
7 days
Anti-platelet drugs
Aspirin
Clopidogrel
Dipyridamole
Platelet and coagulation disorders that cause microangiopathic hemolytic anemia
DIC
TTP
Hemophilia A
Factor VIII deficiency
- Joints and soft tissue bleeding
- Painful hemarthroses and muscle hematomas
- Pressure = necrosis
- Pseudotumors
Abnormal test in Hemophilia A
PTT
Factor VIII clotting assay
Hemophilia B
Factor IX deficiency
Abnormal PTT
Von Willebrand Disease
- Decreased platelet ADHESION
- Premature VIII destruction
- Type 1 is partial deficiency, most common
Abnormal tests in Von Willebrand’s disease
- Elevated PTT
- PFA-100
Vitamin K deficiency affected factors
II
VII
IX
X
Proteins C and S
Abnormal tests in vitamin K deficiency
Prolonged PT and PTT
Abnormal tests in DIC (4)
- Decreased platelets
- Decreased fibrinogen
- Increased PT
- Increased D-dimers
DIC mechanisms
Increased thrombin activity
+ plasmin = fibrinogen and factor depletion
MCV normal values
80-100 fL
Hb normal values
13.5 - 17.5 g/dL male
12-16 g/dL female
MCH normal values
25.4 - 34.6 pg/cell
Reticulocyte count normal value (%)
0.5 - 1.5%
Hematocrit normal values
41 - 53% males
36 - 46% females
Iron deficiency anemia iron values
Decreased:
- Serum iron
- Ferritin
Increased:
- Iron-binding capacity TIBC
Normal iron values (serum, ferritin, binding capacity)
Serum iron: 10 - 30 mmol/L
Serum ferritin: 40 - 340 mg/L ; 14 - 150 mg/L
Iron-binding capacity: 40 - 70 mmol/L
Anisocytosis
Size variation
Poikilocytosis
Shape variation
Iron form absorbed by enterocytes
Fe2+ = ferric
Iron form in the bloodstream
Fe3+ = ferrous
Platelet normal levels
150,000-450,000
ITP effects
IgG remove platelets in 7-10 days or hours
Increase in megakaryocytes
GPIIb/IIIa or GPIb antibodies
Children post-vax or chicken pox or mono infection
ITP treatment
Corticosteroids
IVIG
Immunosuppression
Rituximab
Splenectomy if <30,000
TTP characteristics
- Familial or acquired
- Metalloprotease deficiency, breaks vWF multimers
Microvascular thrombosis = less platelets, hemolytic anemia, fever, renal, neuro, increase LDH, schistocytosis
_____ (PT/PTT) is used as a vigilant for heparin
PTT
When is PT abnormal?
Options: TTP, hemophilia A, hemophilia B, Von Willebrand disease, vit K deficiency, DIC
- Vit K deficiency
- DIC
When is PTT abnormal
Options: TTP, hemophilia A, hemophilia B, Von Willebrand disease, vit K deficiency, DIC
- Hemophilia A
- Hemophilia B
- Von Willebrand disease
- Vit K deficiency
- DIC
In which diseases are MACROCYTES seen?
Liver disease
Alcoholism
Megaloblastic anemia (B12 or folate deficiency)
In which diseases are TARGET CELLS seen?
Iron deficiency
Thalassemia
Liver disease
Hemoglobinopathies
Splenectomy
In which diseases are STOMATOCYTES seen?
“Mouth cells”
Liver disease
Alcoholism
Hemolytic anemias
In which diseases are PENCIL CELLS seen?
Iron defficiency
In which diseases are ECHINOCYTES seen?
“Burr cells”
Liver disease
Splenectomy
Uremia
Pyruvate kinase deficiency
In which diseases are SPHEROCYTES seen?
Hereditary
Autoimmmune hemolytic anemia
Septicemia
Blood transfusion reaction
In which diseases are RBC FRAGMENTS seen?
DIC
Microangiopathy
HUS
TTP
In which diseases are SCHISTOCYTES seen?
Microangiopathic hemolytic anemia
Mechanical damage
In which diseases are DACROCYTES seen?
Myelofibrosis
Thalassemia
Splenomegaly
In which diseases are SICKLE CELLS seen?
Sickle cell anemia
Hypoxia
Hepcidin function
Inhibits Fe release from MQ and ECs
Iron deficiency anemia clinical
- Glossitis
- Angular stomatitis
- Koilonychia
- Dysphagia
- Pica
- Irritable children
Iron deficiency anemia causes (4)
- Blood loss
- Demand increase: infancy and adolescence, pregnancy, lactation, menstruation >80mL
- Gluten enteropathy, gastrectomy, atrophic gastritis
- Poor diet (rare)
How long does it take to replenish iron storage?
At least 6 months
Increase 2 g/dl every 3 weeks
Anemia of chronic disorders iron labs
Decreased:
- Iron
- Iron-binding capacity TIBC
- Reticulocytes
Increased:
- Ferritin
RBC in anemia of chronic disorders
Normo normo
Anemia of chronic disorders pathogenesis
More HEPCIDIN = less release of iron
- Ferroportin degradation
Or less RBC lifespan
NON PROGRESSIVE, relates to disease severity
Sideroblastic anemia
Iron granules not randomly distributed, ringed
Lead poisoning and anemia
Inhibition of heme and globin synthesis
Hypochromatic, hemolytic
Ring sideroblasts
Increased free protoporphin
Anemias classified by size
Micro:
- Iron def.
- Thalassemia
Normo:
- Chronic disease
- Blood loss
- Hemolytic
Macro:
- Folate or B12 def.
- Liver disease
Megaloblastic vs non megaloblastic anemia
Megaloblastic: defective DNA synthesis, hypersegmented neutrophils, B12/folate def.
Non: liver disease, hemolytic, cytotoxicity, etc.
Labs in megaloblastic anemia
Decrease:
- Reticulocytes
- WBC
Increase:
- Unconjugated bilirrubin
- LDH
Why is B12/cobalamine necessary?
It binds to cubilin or amnionless —> endocytosis of IF-B12 at ileum
Transcobalamins —> bone marrow
Aids in DNA synthesis
Megaloblatic anemia clinical findings
Typical anemia symptoms +:
- Purpura
- Vitiligo
- Infertility
- Peripheral neuropathy
- Gastritis
- Depression, psychosis
What is pernicious anemia?
Lack of B12
- Gastric atrophy
- Decreased IF
- Increased gastrin
Folate deficiency causes
- Malnutrition: chronic alcoholism
- Malabsorption: enteropathy
- Increased requirement: pregnancy, hemolytic anemia
- Meds: anticonvulsants, barbiturates, sulfonamides, methotrexate, phenytoin, TMP
Bone marrow in hemolytic anemia
Hyperplasic
Lab findings in hemolytic anemia
Increased:
- Reticulocytes
- Serum bilirrubin
- Urine Urobilinogen
- LDH
- Cholesterol
NO serum haptoglobins
- Hemoglobinemia
- Hemoglobinuria
- Hemosiderinuria
- Methamalbuminemia
Hereditary causes of hemolytic anemia (5)
- Spherocytosis AD can’t pass through spleen
- Elliptocytosis
- G6P dehydrogenase def. XL = oxidative stress (asymptomatic, females with malaria resistance)
- Glutathione def. = prickle cells, like G6P
- Hemoglobin synthesis —> sickle cell anemia (b-globin)
Acquired hemolytic anemia (5)
- Autoimmune: keep warm to avoid
- Alloimmune - ABO and Rh
- Drug: penicillin, rifampicine, methyldopa
- Others: fragmentation, march hemoglobinuria, infections, chemical, physical, secondary
- Paroxysmal nocturnal hemoglobinura XL = less GPI
Hemolytic anemia clinical manifestations (6)
- Typical
- Splenomegaly
- Dark urine
- Ankle ulcers
- Aplastic crises - parvovirus
- Pigment gallstones
Sickle cell anemia crisis (4)
- Vaso-occlusive: infection, acidosis, dehydration = bone infarcts with severe pain hands and feet, lung & spleen
- Visceral: blood pooling/sequestration in chest, liver, spleen
- Aplastic: parvovirus or folate def.
Less reticulocytes - Hemolytic: increase in reticulocytes, painful
Sickle cell clinical manifestations are typical for hemolytic anemias + ______ (7)
- Lower leg ulcers = local ischemia
- Pulmonary HTA
- Tricuspid regurgitation
- Retinopathy
- Kidney papillary necrosis
- Nocturnal enuresis
- Osteomyelitis
What type of hemoglobin do patients with sickle cell anemia have?
F
Sickle cell anemia treatment (7)
- Avoidance
- Folic acid
- Nutrition, vaccines, penicillin
- Crisis: rest, warm, hydration, analgesia
- Transfusions
- Hydroxycarbamide increases HbF
- Stem cell transplant
