Topic 2 - Blood Disorders Flashcards
Where do one third of the body’s thrombocyte reserves remain?
In the spleen in reserve.
What are the three essential plasma proteins?
Albumin - maintaining blood pressure/volume
Globulin - Transportation of bilirubin, lipid and steroids
Fibrinogen - Inactive form of fibrin, necessary for blood clotting.
What volume of blood is in a healthy person? What should the formed part to plasma ratio be?
4-6 L in healthy adult. Approximately 45% is blood cells and 55% is plasma.
All formed elements of blood (with the exception of lymphocytes) derive from which stem cell?
Myeloid stem cell.
What is a CBC? What are its limitations?
A complete blood count is used to determine the number of RBCs, WBCs, and Platelets per unit of blood.
Cannot show abnormalities in cells present, a blood smear is needed for this.
What is a WBC?
A white Blood Count is a measure of the relative percentages of the individual WBC type.
What is a MCV? What kinds of things can it diagnose?
A mean corpuscular volume can determine the volume of the average RBC. Can diagnose megaloblastic or microcytic anemia.
What are the downstream effects of long-term anemia?
Long-term reduction to oxygen capacity can lead to tissue hypoxia and compensatory mechanisms to to restore tissue oxygenation. Such as:
–> Increased heart rate, cardiac output, and circulatory rate
–> preferential blood flow to vital organs.
What would a mean corpuscular hemoglobin concentration or mean cell Hb Concentration (MCHC) be used for?
To test for Hb concentration of RBCs present
Why would one test for the percentage or reticulocytes present?
To show health on bone marrow and determine how many new RBCs are being produced.
What is the definition of anemia?
A reduction in the total number of erythrocytes or a decrease in the quality or quantity of hemoglobin.
Why might erythrocytes be microcytic?
Because there is a shortage of hemoglobin.
What kind of anemia is macrocytic and normochromic? Why?
Anemia caused by folate or b12 deficiency - pernicious anemia
Cells are unable to undergo DNA replication step of mitosis. Become large in preparation of cytokinesis but are never able to separate due to lack of DNA replication.
Which three categories can the effects of anemia be sorted into?
- Manifestations of impaired oxygen transport and the resulting compensatory mechanisms
- Reduction in RBC indices and hemoglobin levels
- Signs and symptoms associated with the process that is causing anemia
How do the kidneys respond to tissue hypoxia?
Releasing EPO and increasing renin-aldosterone –> salt and H2O retention
Increased stroke volume due to tissue hypoxia can lead to which cardiovascular complications?
Hyperdynamic circulation can lead to cardiac murmur and heart failure.
How does long-term hypoxia affect the liver?
fatty changes might occur - such changes might also occur in the heart and kidneys
What is BPG? What is its relevance to anemia?
A molecule and decreases Hb’s affinity for oxygen. Increased levels in those with anemia.
What are the symptoms of mild anemia?
Usually none, but elderly individuals with CV or pulmonary disease may have symptoms.
What are the symptoms of mild to moderate anemia?
Fatigue, generalized weakness, loss of stamina, tachycardia and exertional dyspnea
What are the symptoms of moderate to severe anemia?
–> Orthostatic and generalized hypotension, vasoconstriction, pallor.
–> Tachycardia, dyspnea
–> Angina pectoris, heart failure, transient murmurs
–> Intermittent claudation, night cramps
–> Headache, lightheadedness, and faintness
–> Tinnitus
Which kind of anemia are usually accompanied by jaundice? Why?
Hemolytic anemias - heme breaks down into bilirubin faster than the liver can metabolize it.
Which kind of anemia is usually accompanied by petechia and purpura? Why?
Aplastic anemia - decreased platelet function leads to slower healing of micro tears under skin.
What is aplastic anemia?
A disorder of the pluripotent bone marrow stem cell - leads to a reduction of all three hematopoietic cell lines (aka pancytopenia)
What kind of anemia presents as normocytic and normochromatic?
Aplastic anemia.
Weakness, fatigue, pallor, increased susceptibility to infection, and petechia, and bleeding from mucous membranes is characteristic of what kind of enemia?
Aplastic
What are the three kinds of aplastic anemia?
Primary acquired, secondary acquires (chemo, radiation, toxic chemical exposure, some mycobacteria or virus), and genetic alterations (fanconi anemia)
What is Fanconi anemia?
Aplastic anemia (pancytopenia) due to DNA repair defects.
How is aplastic anemia diagnosed?
- Patient history
- CBC - low and reticulocytes should be close to 0
- Bone marrow biopsy - hypocellular marrow replaced by fat, absence of progenitor cells.
How is aplastic anemia treated?
- Manage symptoms (transfusion of PRBC or platelets)
- Bone marrow transplant (80-85% curative rate)
- Without a suitable donor - immunosuppression therapy
Why is it important to take a patient history when you suspect aplastic anemia?
A history of cancer treatment, chemical exposure, or infection can indicate secondary aplastic anemia.
What is the risk when putting a person with 1° aplastic anemia on immunosuppresants?
They are already immunocompromised - they will be highly susceptible to infection.
What kind of RBC, WBC, and platelet indices would be expected in an individual from anemia of chronic renal failure?
RBC - low due to lack of EPO
WBC - not affected
Platelet - not affected
How would the blood cells of a person with pernicious anemia look?
–> RBCs will be macrocytic
–> Granulocytes are hypersegmented.
–> Platelets are decreases and increased megaloblasts
Because blast cells are unable to replicate DNA to complete mitosis
What might cause B12 deficiency?
–> Damage or atrophy of parietal cells
–> Resectioning of the stomach or small intestine
—> chronic malabsorption in severe Chron’s or AIDS
What might cause folate deficiency?
Dietary deficiencies, alcoholism, cirrhosis, pregnancy, or infancy.
What are some signs and symptoms of vitamin b12 or folate deficiency?
Pedal edema, dyspnea, tachycardia, heart congestion, glossitis, weight loss
Irritability, memory impairment, perversions of smell, taste, and vision, depression, disruption of sleep, personality changes.
What is megaloblastic madness?
Paranoia, delusions, hallucination, and cognitive dysfunction associated with vitamin b12 or folate deficiency
How is folate or vitamin b12 deficiency treated?
- Recognize that megaloblastic anemia is present
- Ascertain which vitamin is deficient and supplement
- Diagnose the underlying disease or mechanism responsible
What kind of anemias are characterized by normocytic and normochromic RBCs, with an increases number of reticulocytes?
Hemolytic anemias
Which kind of anemias are associated with normal WBC count, varied platelets, and microcytic hypochromic RBCs?
Iron deficiency anemia (IDA)
What are some causes for IDA?
Increased demand (pregnancy), insufficient uptake, decreased absorption or chronic blood loss, or genetic conditions (Iron Refraction IDA)
What are some specific symptoms of IDA?
–> Pallor of skin or mucous membranes
–> Koilonychia
–> Glossitis
–> Pica
How do you diagnose for IDA?
- Check RBCs #
- Iron studies: Serum iron, % saturation, and ferritin will be low. Total Fe Capacity of transferrin will be very high (Bc three’s nothing for it to bind to).
What is the normal level of iron % saturation?
33%
How can IDA be treated?
–> oral supplement of iron salts (Iron sulphate is most common)
–> If this doesn’t work, intravenous ferric gluconate, and determine and treat the underlying cause.
What is Pancytopenia?
Low RBCs, WBC, and platelets. Characteristic of aplastic anemia.
Premature destruction of RBCs, retention of body iron and other products of Hb destruction, and an increase in erythropoiesis are all characteristics of which kind of anemia?
Hemolytic anemias
Hemolytic anemias display which kind of RBC?
Normocytic and normochromatic
Where does the majority of hemolysis occur?
Intravascularly in the spleen
What is thalassemia?
A set of genetic disorders associated with inhibition of globin chain synthesis. May affect the alpha or beta chain, and is named accordingly. In response to this, the other (now unpaired chain) builds up in cell in excess.
Which two factors lead to anemia in someone with thalassemia?
- Decreased Hb due decreased synthesis of affected chain –> decreased erythropoiesis
- Excess of unpaired chains –> precipitation in RBC –> Hemolysis
Which longterm complications are seen in those with thalassemia? Why?
Iron overload and Liver Toxicity
–> Increased EPO causes the body to absorb more iron (but it isn’t actually losing any from the hemolysis)
Bone Deformity
–> Cortical bone is transformed into spongy bone to produce more blood cells. Bone becomes fragile.
All deformities area a result of EPO released from kidneys in response to anemia.
In someone with thalassemia, what would you expect from a CBC and MCV?
CBC - decreased RBCs due to hemolysis, Platelets and WBCs normal
MCV - Decreased due to decreased Hb
What is Sickle Cell Disease?
An inherited, autosomal recessive disorder caused by a mutation in the Beta globin gene leading to abnormal Hb - HbS instead of HbA.
a Glu in the beta chain is replaced with Val, due to a mutation on the DNA.
What is the difference between major and minor thalassemia?
Minor - heterozygous carrier state
Major - homozygous state, accumulation of unpaired chain seen.
How is thalassemia treated?
Blood transfusion, iron chelation, or a splenectomy as needed.
Longterm a bone marrow transplant can help.
Why is the sickle cell gene more common in sub-Saharan African population?
Because the gene provides some immunity against malaria.
What might cause a person with SCD to go into crisis?
Stress such as hypoxemia, decreased pH, low temperature, or decrease in plasma volume
What are the clinical manifestation of SCD?
–> Severe anemia (and chronic hyperbilirubinemia
–> Vessel Occlusion and chronic pain
–> Heart chamber enlargement + myocardial infarction
–> Splenomegaly, hepatomegaly, hypogonadism
What causes chronic pain in those with SCD?
A build up of lactic acid that cannot be transported due to sickled cells and vessel occlusion
What causes heart chamber enlargement in someone with SCD?
Enlargement caused by increased output due to chronic anemia
What might cause splenomegaly or hepatomegaly in someone with SCD?
Enlargement due to sickle cell accumulation, organs become engorged with sickled cells and blood.
How is a sickle cell crisis treated?
Rehydration therapy to reverse the dehydration and hypoxia during a vaso-occlusive crisis.
Blood transfusions to replace sickled cells with healthy RBCs
Chronic pain manages using NSAIDS, acutely painful episodes managed with morphine.
How can sickle cells crises be prevented?
Preventing infections, cold, and dehydration.
Infections treated with antibiotic prophylaxis and early immunization for pneumococcus and meningococcus infections.
When is hydroxyurea prescribed? why?
It is an anti-neoplastic drug that increases the production of HbF that does not sickle.
Why might NO be prescribed to someone with SCD?
It is vasodilator.
What is Hereditary Sphereocytosis?
The most commonly inherited anemia in individuals with Northern European Ancestry.
A dominant trait disorder that causes mutations in genes producing RBC membrane proteins. RBCs become deformed, less flexible, and unable to traverse blood vessels.
What are some clinical manifestations of hereditary spherocytosis?
Jaundice, pallor in infants, splenomegaly, leg ulcers, bilirubin, gallstones.
Why are leg ulcers common in those with hereditary spherocytosis?
lack of bloodflow to injured areas leads to inhibited repair.
How can hereditary spherocytosis be treated?
Blood transfusion in crisis and a splenectomy if necessary.
What is hemolytic disease of the newborn?
When a Rh- female gives birth to an Rh positive child, her body produces antibodies against the fetus’s blood type.
A second pregnancy with a fetus with another Rh+ child will result in her immune cells attacking those of the fetus.
How is hemolytic disease of the newborn treated?
RhoGAM, and in severe cases, in utero blood transfusions and early delivery.
What blood cell indices would you expect to see in someone with hemorrhagic anemia?
Normal indices + smaller blood volume
What is a healthy hematocrit?
> 47% in women, and >54% in men
Describe both types of absolute polycythemia.
Secondary
–> chronic hypozemis (COPD, Smoking)
–> Physiological increase in EPO (such as in high altitudes)
–> EPO doping
Vera
–>neoplastic (or myoproliferative) disorder that affects all cells of progenitor stem cell.
What is relative polycythemia?
Increased hematocrit due to decrease in plasma volume with no change in # of RBCs.
How would one determine if polycythemia was relative or absolute?
RBC mass + Hb will be increased in someone with absolute polycythemia.
They will be completely normal in someone with relative polycythemia.
How would one tell the difference between secondary and polycythemia vera?
Secondary will be due to increased EPO presence, and the underlying cause of that must be treated.
Vera is caused by stem cell issue, so EPO levels will be normal.
How can polycythemia vera be treated?
Characterized by increased RBCs, WBCs, and platelets.
Blood letting and chemotherapeutic agents can help.
What are the symptoms of polycythemia?
Increased blood viscosity leads to headache, dizziness, weight loss, thrombosis, chronic hypoxia, hypertension.
What are the steps of hemostasis?
- Vasoconstriction
- Formation of a platelet plug within 3-7 minutes
- Secondary hemostasis involves formation of fibrin clot (coagulation)
- Fibrinolysis
Describe the process of triggering the Intrinsic coagulation pathway.
Factor XII is activated by coming in contact with endothelium collagen or another negatively charged surface. This triggers a cascade involving factor XI, IX, and VIII, which triggers factor X –> prothrombin to thrombin –> fibrinogen to fibrin.
Describe the process of triggering the extrinsic coagulation pathway.
Tissue factor (released from damaged cells) triggers factor VII which triggers factor X –> prothrombin to thrombin –> fibrinogen to fibrin
Which lab tests are used to determine if someone has a disorder of hemostasis?
Bleeding time - evaluates vascular status and platelet function
PT/INR (Prothrombin Time) - Evaulates how long it takes a sample of blood to clot after the addition of tissue extract (extrinsic pathway)
aPTT (Activated Partial Thromboplastin Time) - Time is takes a sample to clot after addition of compounds that mimic contact of blood with an artificial surface (intrinsic pathway)
Are platelet disorders…
more common in women or men?
More often acquired or inherited?
Women
More commonly acquired
Are coagulation disorders…
more common in women or men?
More often acquired or inherited?
Men
More commonly congenital
What is thrombocytopenia?
A decreased platelet count
What are some causes of thrombocytopenia?
Cancer treatment, B vitamin deficiency, aplastic anemia.
Decreased survival might be due to infection, splenic sequestration or immune attack.
Platelet dilution is due to massive blood transfusions stored more than 24 hours.
What is Immune Thrombocytopenia Purpura (ITP)?
An immune mediated thromocytopenia.
Can be Acute…
–> more common in children
–> Lasts 1-2 months following an acute viral infection
…Or chronic
–> autoantibodies against platelet specific antigens
–> usually developed between 2-40 years
–> Tends to get worse
–> Can be treated with immunosuppressants
What are some clinical manifestations of thrombocytopenia, from mild to severe?
–> symptoms absent until about 100,000/µL
–> Petechiae / purpura at 50,000/µL
–> Spontaneous mucosal, deep tissue, and intracranial bleeding
–> visceral hemorrhage
–> intracranial hemorrhage is most severe and fatal
How is thrombocytopenia diagnosed?
–> CBC (low platelets)
–> Prolonged bleeding time
–> PT/INR & aPTT are normal
–> Review of all medication being taken
How might thrombocytopenia be treated?
Discontinuation of drugs and avoidance of aspirin or other blood thinners.
Spleen is major site of platelet destruction and antiplatelet bodies, so a splenectomy might be necessary.
What is thrombocytosis?
High numbers of platelets in blood (>400,000/µL)
What are the three kinds of thrombocytosis?
Transitory - stress of physical exercise triggers the release of preformed platelets
Secondary (reactive) - Increased platelet production due to unknown mechanisms (could be hypersplenism, hemorrhage, or iron deficiency
Primary (essential) - Increased megakaryocyte proliferation (could be caused by myoproliferative disease such as polycythemia vera or CML)
How is thrombocytosis treated?
Only the primary etiologies require direct treatment of thrombocytosis. Cytotoxic agents, antiplatelet or interferon therapy.
What are coagulopathies?
Defects of normal clotting mechanisms.
What is hemophilia?
A group of hereditary disorders (the most common inherited bleeding disorder) associated with clotting factor VIII (A, 85%) or IX (B, Christmas disease). (both are issues with intrinsic pathway)
X linked disorder affects primarily boys.
What is a hallmark of hemophilia?
Hemarthroses - hemorrhage within a joint (such as knees, elbows, or ankles)
Extremely painful and can lead to progressive destruction of cartilages and joints –> arthritis.
What would you expect from the following lab results in a person with hemophilia?
–> Platelet count
–> Bleed time
–> Pt/INR
–> aPTT
Normal platelt count
Normal bleeding time
Extrinsic pathway functioning normally
Intrinsic pathway delayed
How is hemophilia treated?
A - factor VIII concentrate or cryoprecipitate
B - Fresh frozen plasma or cryoprecipitate
What is Von Wilibrand disease?
A decrease of absence of von Willibrand factor and factor VIII. Makes it harder for platelets to stick to an area and form a clot.
Describe the relationship between VWF and factor VIII
The two circulate together as a complex; VWF is necessary for stabilization of Factor VIII.
Which results would you expect on a coagulation test for someone with Von Willebrand disease?
–> Prolonged bleeding time
–> Increased aPTT
–> Normal platelet count
–> normal PT/INR
How is von Willebrand disease treated?
Desmopressin
–> Releases VWF & factor VIII from vascular endothelial cells
Avoid NSAIDS (inhibit platelets from clotting)
How does a Vit K deficiency affect blood coagulation?
Vit K is needed for the synthesis of coagulation factors II, VII, IX, and X. Without it, bleeding disorder occurs.
What are the two ways Vit K defefiency is acquired?
Bleeding in infancy occurs because an infant’s liver is not yet fully formed to synthesize factors. Additionally, an infant’s microbiota might not be fully formed, and they therefore cannot synthesize vitamin K.
Acquired Vit K deficiency occurs in adulthood due to malabsorption, chronic hepatic disease, antibiotic therapy, or malnutrition.
What is done to prevent Vit K deficiency and bleeding in infancy?
Newborns are administered Vit K injections within 6 hours of delivery.
What coagulation test results would be seen in someone with a Vit K deficiency?
PT/INR increased but all others normal.
This is because factor VII has the shortest half life, and therefore its deficiency is noticed first. Eventually the aPTT will increase as well.
How is Vit K deficiency treated?
–> Administer Vit K
–> Plasma transfusion for those with severe hemorrhage
What is Disseminated Intravascular coagulation?
Complex, acquired widespread coagulation, which consumes all clotting factors and causes bleeding in vascular compartments.
What are the two kinds of DIC?
Chronic (primary) occurs in cancer patients with malignancy
Acute (secondary) occurs due to sepsis, snake bite, trauma, or crush injuries.
What is the most common condition associated with DIC?
Sepsis
What are the signs and symptoms of DIC?
–> Bleeding (petechiae, ecchymoses on skin and mucous membranes, bleeding into orifices)
–> Cold, mottled fingers and toes due to microthrombi
–> Dyspnea and crackles
–> Possibility of acute renal failure due to thrombi in renal microvasculature.
What results to coagulation tests would be seen in someone with DIC?
–> Decreased platelet count and fibrinogen concentration (which can be quantified by counting D dimers)
–> prolonged bleeding PT/INR, and aPTT
How is DIC treated?
Correction of underlying cause and support major organs
Plasma, PRBCs, platelets, or cryoprecipitate
Heparin might be used to prevent further coagulation and microthrombi (but this is controversial and might further exacerbate other wing of disease.
