What are the 4 stages of a clot formation?
1) vasocontriction 2) platelet plug formation 3) Coagulation 4) fibrinolysis
what occurs during the vasoconstriction stage of clot formation?
Diminishes blood flow and loss
What do platelet granules relase to induce vasoconstriction during clot formation?
What three factors occur to allow a platelet plug formation to occur?
1) collagen 2) ADP 3) Thromboxane A2
What does collagen do to help create a platelet plug?
Collagen promotes the platelets to adhere d/t vWF
What is vWF?
Von willebrand factor which is the portion of the platelet that causes adhering of the platelet to the damaged area
What does ADP do to help create a platelet plug?
ADP attracts more plateles
What does Thromboxane A2 do to help create a platelet plug?
thromboxane promotes aggregation, degranulation and vasoconstriction
what is the most common inherited bleeding disorder?
Von willebrand disease (lack of vWF)
What are the two pathways of the coagulation stage of a clot formation?
intrinsic (APTT) and extrinsic pathway (PT)
what happens in the fibrinolysis phase of the clot formation?
Plasminogen is activated by plasminogen activators (both nonfibrin-specific or less fibrin-specific) in order to degrade fibrinogen
What kind of condition occurs when fibrinolysis is compromised?
An emergency situation
what basic routine laboratory test categories can be used to evaluate the ability to form a clot?
1) vasocontriction 2) platelet plug formation 3) Coagulation
what basic routine laboratory tests can be used to evaluate the vasoconstriction ability to form a blood clot?
what basic routine laboratory tests can be used to evaluate the platelet plug formation ability to form a blood clot?
1) Platelet Count 2) Bleeding Time (BT)
what basic routine laboratory tests can be used to evaluate the vasoconstriction ability to form a blood clot?
1) Prothrombin Time (PT) 2) (activated) Partial Thromboplastin Time (APTT, PTT)
Is blood clotting the same as coagulation?
No, coagulation is a phase of blood clotting
What category of basic laboratory test is used to evaluate the ability to remove a blood clot when it is no longer needed?
What fibrinolysis category basic laboratory test is used to evaluate the ability to remove a blood clot when it is no longer needed?
Fibrin degradation products (FDP, D-dimer)
What type of test is a bleeding time?
primarily a platelet function test
What does the bleeding time evaluate?
Evaluates interaction of platelets with vessel wall and formation of the platelet plug
Does the bleeding time function dependent of coagulation or independent of coagulation?
functions independent of coagulation
What condition will prolong bleeding time?
Thrombocytopenia (<100K, definitely , 50K)
What must be established in order for a bleeding time to be used as a platelet function test?
a normal platelet count must first be established
will the bleeding time remain normal in hemophilia?
what term is used to decribe an increased amount of time over normal for any “time” test?
what aspect can affect BT?
Vasoconstriction capabilities therefore it is not suited for patients with senile skin changes
what are the two routine methods of performing a BT?
1) Duke Bleeding Time 2) Ivy Bleeding Time
Where does the stab wound occur in the Duke Bleeding Time?
stab wound to the ear lobe
Where does the stab wound occur in the ivy Bleeding Time?
more standardized method of incision to the forearm
what are some factors that may affect Bleeding time?
1) Poor vascular function 2) Depth of incision 3) Touching incision 4) ETOH consumption 5) Aspirin consumption (5 days after one 300 mg dose)
What are the most common causes that prolong the bleeding time?
1) Quanitative platelet abnormalities (thrombocytopenia) 2) Qualitative platelet abnormalities (platelet function) 3) loss of capillary integrity
what are two reasons for thrombocytopenia?
1) Reduced production in the bone marrow 2) destruction of platelets outside the bone marrow (intravascular or intrasplenic)
What would be the cause of qualitative platelet abnormalities (platelet function)?
von willebrand’s disease
What would be the cause of qualitative loss of capillary integrity?
1) collagen vascular diseases 2) Senile capilary fragility
What is a platelet count?
part of a routine CBC
When will spontaneous bleeding occur due to platelet count issues?
Anytime platelet count falls below 40-50K
What is the most common cause of thrombocytopenia?
1) Reduced production in the bone marrow 2) destruction of platelets outside the bone marrow (intravascular or intrasplenic)
what can cause a reduced production of platelets in the bone marrow?
1) Bone marrow malignancies (both primary and metastasis destroys normal bone marrow) 2) Toxic effects of drugs, chemicals and microorganisms 3) Factor deficiencies (B12 and folate)
can thrombocytopenia cause spontaneous bleeding?
No, it just prevents clotting
what can cause an increased destruction of platelets outside the bone marrow?
Intravascular and intrasplenic immune reactions (ie: idiopathic thrombocytopenic purpura)
What is an activated partial thromboplastin time?
The time it takes a plasma specimen to yield a fibrin clot once the intrinsic Pathway is initiated
What is the difference between APTT and PT?
APTT is a screening test of the intrinsic pathway whereas PT is a screening test of the extrinsic pathway
A patient on what medication will require an APTT to monitor their condition?
patients on therapeutic heparin for monitoring purposes
What are the most common causes of prolonged APTT?
1) congenital coagulation factor deficiencies 2) Acquired coagulation factor deficiencies 3) Anticoagulant medications
What congenital coagulation factor deficencies can prolong APTT?
Hemophilia A and B
What factor is Hemophilia A deficient?
What factor is Hemophilia B deficient?
What is an acquired coagulation factor deficiencies that can commonly cause prolonged APTT?
Chronic liver disease (hepatic insufficiency results which implies liver damage is beyond repair)
What anticoagulant medications commonly cause prolonged APTT?
Heparin and coumadin (PT is better)
What is a Prothrobin time (PT)?
The time it takes a plasma specimen to yield a fibrin clot once the extrinsic Pathway is initiated
What is an INR?
International Normalized ration (INR) which uses the PT and creates a ratio to account for inter-laboratory variability in PT
What are the most common causes of a prolonged PT?
1) Congenital coagulation factor deficiencies 2) Acquired coagulation factor deficiencies 3) Anticoagulant medications 4) Vitamin K deficiency
What congenital coagulation factor deficencies can prolong PT?
The only factor is VII and it is uncommon
What acquired coagulation factor deficiences can commonly cause a prolonged PT?
chronic liver disease
what will prolong earlier due to liver disease, PT or APTT?
PT prolongs before the APTT
what anticoagulant medications commonly cause prolonged PT?
coumarin (using the INR)
What are the 2 ways in which we have the inability to regulate hemostasis?
- Hemorrhage. 2. Thrombosis.
What type of state is thrombosis?
what is a D-Dimer assay?
D-Dimer is a fibrin degradation product
what is D-Dimer used for?
As a screening tool for DVTs
What is the definitive diagnosis of DVT?
venous scanning procedures
when should patients be referred for a venous scanning procedure?
When there is an increased level of D-Dimer in a patient
During what treatement is a d-dimer helpful for monitoring possibility of recurrence of DVTs?
When determining length of anticoagulant treatment.
What are the 2 categories of bleeding disorders?
- Coagulation associated bleeding. 2. Platelet associated bleeding.
What are the 2 types of coagulation associated bleeding?
Inherited and acquired.
How can you tell if a bleeding condition is congenital?
most of the major congenital bleeding disorders are coagulation- associated disorders. Congenital disorders tend to manifest earlier in life.
How should a new vs old bleeding disorder be treated?
New- immediate diagnostic and treatment preferably by a specialist. Old- careful monitoring but no further diagnostic testing.
What is the difference between provoked and spontaneous bleeding?
Spontaneous (unprovoked) bleeding is a serious situation and requires immediate emergency medical referral whereas provoked bleeding is bleeding associated with trauma or surgery that is out of proportion to that expected from the trauma or surgery
Coagulation-associated bleeding is usually bleeding where?
What is bleeding in joints called? What can repeated joint bleeding cause?
Hemarthrosis. Can cause degeneration as an arthritic change.
Platelet-associated bleeding is usually what?
Mucous membrane, or mucocutaneous bleeding or brusing.
Name different types of brusing?
Petechiae, ecchymosis, purpura.
Genetic bleeding disorders tend to be what type of inheritance?
How can drugs/ medications cause bleeding disorders?
Asprin or certain NSAIDs cause platelet function to be altered. Some drugs can suppress bone marrow production of platelets. Platelet function or production may be affected via idiosyncratic drug reactions.
Name systemic diseases that might cause bleeding disorders?
Recent infections, presence of other hematologic diseases, nutritional deficiencies, autoimmune diseases, liver diseases.
What are signs and symptoms of other hematologic disorders?
Anemia, lymphadenopathy, splenomegaly, bone pain.
Name the 3 congenital coagulation-associated bleeding disorders?
Hemophilia A, Hemophilia B, Von Willebrand’s disease.
What causes Hemophilia A and B?
A- factor VIII:C deficiency. B- factor IX deficency aka christmas factor.
What is the most common severe of the 3 congenital coagulation-associated bleeding disorders?
What is the most common of the 3 congenital coagulation-associated bleeding disorders?
von Willebrand’s disease is the most common inherited hemostatic disorder.
Of the 3 congenital coagulation-associated bleeding diseases will they effect males or females more?
Hemophilia A and B more males. vWD- males equal females.
Where will bleeding most commonly occur at with hemophilia A?
Anywhere, but most commonly into large weight bearing joints (knees, ankles, elbows) and soft tissues.
What are the types of hemophilia A?
Severe, moderate, mild and they depend on the amount of factor VIII:C that is missing.
How common are the 3 types of hemophilia A and what are they like?
Severe (<1%)- evident early in life, spontaneous bleeding for no apparent reason. Moderate (1-5%)- not appatent until child attempts to place weight on large joints. Mild (5-30%)- not noticed until after trauma or surgery.
What is a PT test?
Prothrombin test- testing the extrinsic clotting pathway.
What is a APTT test?
Activated partial thromoplastin time- testing the intrinsic clotting pathway. AKA PTT.
What is a BT test?
Bleeding time- assess platelet function.
What is a platelet count test?
Just a count of total platelets done with a BT test (before you can know if the platelets are functioning normaly you need to know if you have a normal amount).
What are the lab findings for hemophilia A?
Normal- PT, Platelet count, and BT. Prolonged PTT.
With hemophilia A and B will they be caused by factor deficiencies or abnormal functioning factors?
A- deficiency and rarely due to abnormal function. B- 2/3 is deficiency and 1/3 is abnormal function.
What is the most common inherited hemostatic disorder?
Von Willebrand’s Disease
What will the lab findings be for hemophilia B?
Normal- PT, Platelet count, and BT. Prolonged PTT. Same as hemophilia A and they are genetically similar.
vWD is what type of abnormality? Caused by what?
Coagulation and platelet function due to dyfunctional or deficient von willebrand’s factor.
What is the purpose of von Willebrands factor?
mediates platelet adhesion and preserves VIII:C from degradation.
The greater majority of vWD patients only manifest what?
Platelet-associated bleeding (mucocutaneous bleeding - epistaxis, gingival bleeding, menorrhagia; occasional GI bleeding and rarely hemarthrosis)
How many types of vWD are there and which one is most common?
5 subtypes and type I makes up 80%.
What is type I vWD like?
clinically mild quantitative deficiency in vWF.
The most common vWD patient will display what type of bleeding?
Mild provoked bleeding following trauma, surgery, and dental extractions. Some women can have abnormal menstral bleeding.
A type I vWD patient may become more evident when?
With the use of asprin since the asprin will further decrease the platelet’s ability to adhere.
What are the lab results for a vWD patient?
Normal- PT, Platelet count, PTT (rarely prolonged only when VIII:C is <25% of normal and this will not happen with subtype I). Prolonged- BT(occasionally normal, but can be provoked with an asprin challenge).
What are 2 types of aquired coagulation-associated bleeding disorders/
Hepatic insufficiency. Vitamin K deficiency.
What will happen with hepatic insufficiency (Hemostasis related)?
Leads to bleeding tendency due to decreased production of coagulation proteins.
What coagulation factors need Vitamin K?
II, VII, IX, X.
What can lead to vitamin K deficiencies?
Biliary tract disease due to malabsoprtion due to fat absorption problems. Nutritional deficit is rare. Broad-spectrum antibiotics destroy GI flora that normally produce Vitamin K.
Besides coagulation factors what coagulation proteins are important?
Some that inhibit fibrinolysis (continued consumption of coagulation factors).
What causes fibrinogen deficiency?
This is a late effect of a severly compromised liver.
How else will a cirrhotic liver affect hemostasis?
Reduction in thrombopoietin and this leads to thrombocytopenia.
What are the lab findings with early and late hepatic insufficiency?
Early- Normal- APTT, platelet count, BT, prolonged PT. Late- Prolonged PT, APTT, BT, Decreased Platelet count.
What would lab tests be like for a pateint with mild vitamin K deficiency or on theraputic doses of Warfarin?
Both would have normal APTT, Platelet count and bleeding time and Prolonged PT.
What can cause a false vitamin K difficiency?
Vitamin K antagonistic medication like Warfarin
What is INR?
International normalized ratio for patients on Coumadin or Warfarin. PT values are used to monitor patients on oral anticoagulants like coumadin and warfarin.
What are the 2 things that can cause thrombocytopenia?
Bone marrow not making enough platelets or something happens to them once in circulation.
Thrombocytopenia is what type of bleeding disorder?
quantitative (not enough) platelet-associated bleeding disorder.
Name the things that can cause thrombocytopenia due to bone marrow suppression?
1) aplastic anemia (lost ability to produce blood cells) 2) leukemias (normal bone marrow is being replaced with malignant and remaining bone marrow cant keep up) 3) metastatic lymphoma or carcinoma replacing bone marrow 4) folic acid or B12 deficiencies 5) chemotherapy and radiation therapy 6) viral infections (HBV, EBV, HIV, CMV) 7) Drugs (including alcohol).
What is the name of a disease that causes thromobyctopenia due to peripheral platelet destruction?
Idiopathic thrombocytopenia purpura (ITP).
What causes ITP?
Autoimmune phenomenon where IgG mediated antibodies coat platelets resulting in splenic sequestering of platelets.
What type of bleeding will ITP cause?
Mucocutaneous bleeding, epistaxis, bleeding gums, prupura, petechiae, menorrhagia.
Will ITP cause splenomegaly?*
What are the 2 types of ITP?
Acute and chronic.
When will acute and chronic ITP begin? What will the onset be like?
Acute- pediatric and abruptly. Chronic- adult with insiduous onset.
What will cause acute and chronic ITP?
Acute- 80% post viral infection. Chronic- associated with other systemic dieases such as malignancy, other autoimmune diseases, rarely with viral infections.
What is acute and chronic ITP like and How long will acute and chronic ITP last?
Acute- short course markedly reduced platelet count (<20K) then it will spontaneously go into remission. Chronic- longer clinical course up to years with platelet count 20-100K and will rarely spontaneously go into remission.
How can acute and chronic ITP be treated?
Acute- supportive. Chornic- corticosteroids or splenectomy.
What is anemia?
The hematologic state in which the number of RBC, the amount of hemoglobin, and the volume of RBC is less than normal resulting in a pathologic deficiency in oxygen-carrying capacity of blood.
When should anemia be suspected?
1) Mucous membrane pallor (best place to see is conjunctiva since pallor due to anemia is not always pale complection) 2) fatigue 3) generalized weakness 4) dizziness 5) headaches 6) tinnitus (ringing or buzzing in ears) 7) palpitations 8) tissue changes in lips or tounge 9) peripheral neuropathy.
What general populations have higher prevalence of anemia?
1) Pregant 2) elderly over 75 years 3) nutritionally unbalanced diets.
In general what are the reference ranges like for hemoglobin?
Smaller in children and highest in adult males and slightly lower levels in pregnant females vs adult females.
How much fluctuation from the normal reference ranges is allowed for a pregnant female? ( in gm/dL)
1 gm/dL difference ie: if reference range is 12-16 and pregnant patient is 11.4 then this is still acceptable as normal
What are the 2 general ways of classifying anemia?
RBC indicies. Pathophysiology.
What are the 3 types of anemia based upon RBC indicies?
- Microcytic hypochromic. 2. Normocytic normochromic. 3. Macrocytic.
What are the types of microcytic hypochromic anemias?***
1) iron deficiency 2) thalassemias (faultly synthesis of hemoglobin) 3) chronic diseases
What are the types of normocytic normochromic anemias?***
1) hypoplastic bone marrow 2) chronic diseases 3) hemolytic anemias.
What are the types of macrocytic anemias?***
B12 and folate deficiencies.
What are the 3 types of anemias based upon pathophysiology?
1) factor deficiency 2) production defect 3) hemolytic.
What are the factor deficiency anemais?
1) Iron 2) B12 3)folate deficiencies.
What are the production defect anemias?
1) Chronic disease 2) hypoplastic bone marrow.
What 5 things lead to an increased risk of iron deficiency anemia (IDA)?
- Deficient diet. 2. Decreased absorption. 3. increased requirments like growth spurts. 4. Pregnancy. 5. Blood (chronic) loss.
What causes IDA in all adults until proven otherwise?
What 2 types of bleeding often lead to IDA in adults?
Gynecological and GI.
When will signs of IDA be seen?
Late in deficiency due to insiduous nature of onset.
What is peripheral blood like with early decreases in iron storage?
What will peripheral blood be like with depleted storages of iron?***
Early changes will be increased RDW. Decreased RBC, HgB, Hct, and MCV MCH and MCHC decreased.
What will serum iron panel be like with an IDA patient that has not had treatment?***
Decreased; serum iron, % saturation, serum feritin. Increased- TIBC.
What lab change in iron deficiency is the earliest sign of anemia?
Decreased serum ferritin (loss of iron stores) while other tests are normal
What lab change in iron deficiency is a later sign of anemia?
Decreased serum iron, increased TIBC and decreased % saturation (<15%)
With resolution of anemia in what order do the lab tests normalize?
CBC -> Serum iron, TIBC, % sat -> serum ferritin
Would a factor deficient anemia have increased or decreased reticulocytes?
Decreased reticulocytes because there is a decreased amount of nutrients
What type of anemia is iron deficiency?
Microcytic and hypochromic.
What will peripheral blood be like once the depleted storage of iron problem has been fixed, but not replenished?
RBC, HgB, HcT increase. Temperature increases. RDW increases. Indicies increase.
Once treatment for anemia has been initiated what hematology signs should be seen?
Increasing RBC count, hemoglobin concentration, hematocrit, MC, MCH, MCHC and (marked increase in RDW) therefore causing microcytosis (old leftover small RBCs), macrocytosis (newer, healthier RBCs), marked anisocytosis (increased RDW) and polychromatophilia (d/t increased reticulocytosis
When should a reassess of anemia treatment be?
Reassess no sooner than a month but a quicker assessment would be a reticulocyte count where the diagnosis is slightly decreased (is not considered a good diagnostic test)
Once treatment for anemia has been initiated what serum iron panel results should be seen?
Increasing serum iron, % saturation and serum ferritin but a decreasing TIBC
What are some essentials of diagnosis of anemia?
1) Serum ferritin <12mcg/L 2) caused by bleeding unless proven otherwise 3) responds to iron therapy
What is thalassemia?
Anemia caused by faulty synthesis of hemoglobin.
What will serum iron panel be like with an Iron Deficiency Anemia (IDA) patient that has started treatment?
Decreased; TIBC. Increased; Serum iron, % saturation, serum ferritin.
Which iron panel will be the best indication of iron storage?
Serum ferritin and it takes the longest time to return to normal.
What would a typical CBC look like for an IDA patient?
Low HGB and HCT= anemia. Low MCV= microcytic. Low MCH and MCHC= hypochromic.
When you get a CBC that looks like IDA what should be done?
Check for bleeding problems and Order Serum iron studies before iron supplementation starts.
Why should you order serum iron studies first?
It could be from loss of blood not just diet issues.
What would a CBC look like for a Vitamin B12 and Folic acid anemias?
Low HGB and HCT= anemia. High MCV= macrocytic. Normal MCH and MCHC= normochromic.
What are the 2 general types of macrocytic anemias and what causes them?
- Megaloblastic anemai= B12 and Folate. 2. Non-megaloblastic= ethanol, liver disease, hypothyroidism.
From a CBC how can you distinguish a B12 from a folate deficiency?
You can’t, they look identical.
What is B12 used for?
It is needed for the proper utilization of Folic Acid in the synthesis of DNA and therefore both are needed for appropriate cellular growth.
B12 and folate deficiencies result in what?
Ineffective erythropoiesis and marcrocytic cells that will lead to intramedullary hemolysis due to increased size.
B12 and folate deficiencies lead to asynchronous maturation of blood cells which leads to what?
Neutropenia, hypersegmentation of the neutrophils and mild thrombocytopenia (not to the level of spontaneous bleeding).
What are the signs and symptoms of B12 and folate deficiences besides the normal anemic ones?
Neuropsyciatric and GI signs and symptoms.
Where and how is vitamin B12 absorbed?
Must be bound to intrinsic factor and is absorbed in the terminal ileum.
Where will intrinsic factor come from?
Gastric parietal cells.
What is Vitamin B12 and folate acid storage like?
B12- stored in liver and can hold 2-3 years worth of B12. Folate- stored in liver but only 2-4 months worth.
What are the causes of B12 deficiency?
- Diet. 2. Malabsorption. 3. Drugs.
What is the major dietary source of B12?
Meats and dairy (therefore lack of B12 usually in strict vegans)
What are the types of malabsorption that leads to B12 deficiency?
- No intrinsic factor. 2. Gastrectomy. 3. Blind loop syndrome. 4. tape worm. 5. Ileum diseases.
What is pernicious anemia?
An autoimmune condition that will cause gastric mucosa loss and lead to a decrease in intrinsic factor.
How will a gastrectomy cause B12 deficency?
Loss of stomach musoca and cant produce intrinsic factor.
What is blind loop syndrome and how will it affect B12 absorption?
Outpouching of gut and enteric microorganisms overgrow and thrive in the loop and the bacteria here can consume B12.
How will fish tapeworm (Diphyllobothrium latum) lead to B12 deficency?
name a disease of the ileum that affects B12 absorption and why?
Crohn’s disease- if it affects the terminal illeum it can lead to a decrease in B12 absorption.
What drugs will cause a B12 deficiency and how?
1) Alcohol- can lead to gastritis and damage the lining and interfere with intrinsic factor production. 2) Nitrous oxide- prolonged use can damage bone marrow and nervous system by interfering with the ACTION of B12.
What are some hematology lab findings with Vit b12 deficiency?
1) Anemia 2) Macro-ovalocytic RBCs 3) Leukopenia (neutropenia) 4) Hypersegmented neutrophils 5) Thrombocytopenia (mild)
How do the hematology lab findings differ between B12 and folate deficiency?
They don’t, they are the same for both
What would routine serum chemistry tests show for a B12 or folic acid anemia?
Unconjugated hyperbilirubinemia and increased LDH. Both of these will come as a result of RBC lysis since they are macrocytic.
What tests can be done if you suspect B12 deficiency?
Serum Vitamin B12. Serum methylmalonic acid (MMA).
A patient with B12 deficiency will have what results from a serum B12 and a MMA test?
Serum B12- decreased and MMA- increased.
What is the relationship with MMA and B12?
Without B12, MMA levels go up because B12 is required (coenzyme) for MMA to be converted to the next stage on its path to making folic acid. The increased MMA may be seen before serum B12 levels go down.
If you know a patient has a B12 deficiency what tests can be done to determine if it is pernicious anemia?
Schiling test if positive is due to lack of intrinsic factor but is not specific for pernicious anemia so you can run a anti-intrinsic factor and anti-gastric parietal cell antibody tests.
What will anti-intrinsic factor and anti-gastric parietal cell antibody tests screen for?
both for pernicious anemia. Anti-intrinsic factor is (60% specific for pernicious anemia) and anti-gastric parietal cell antibodies are (90% specific for Pernicious Anemia).
What are the clinical features that are common to both B12 and Folate deficiencies?
Megaloblastic anemia, fatigue, weight loss, diarrhea, loss of appetite, fever, sore tongue, jaundice, fundal hemorrhages in severe cases.
What are the clinical features that are common to just B12 deficiency?
Parestheisa, dementia, neuropathy, demyelination of spinal cord.
Wha tare the clinical features specific to pernicious anemia?
family or personal history of vitiligo, autoimmune thyroid disease.
What would jaundice skin look like due to anemia?
Lemon-yellow due to pallor and jaundice.
What are some vague GI symptoms following B12 deficiency anemia?
1) Glossitis, burning, beefy tongue 2) Anorexia 3) Diarrhea
What are some neuropsychiatric symptoms following B12 deficiency anemia?
1) Peripheral neuropathies (distal parasthesias especially lower extremities) 2) Dorsal column symptoms (vibratory and position sense abnormalities, balance difficulties) 3) Mood alterations, depression, dementia
Name 4 things that can cause a Folic acid deficiency?
- Dietary insufficiency. 2. Malabsorption. 3. Drugs. 4. Increased requirements.
What can cause dietary insufficiency of folic acid?
1) impoverished and elderly populations 2) anorexic patients 3) inadequate fresh fruits, vegetables and grains 4) overcooking fruits and vegetables
What types of foods have folic acid?
Fresh fruits, vegetables and grains. (not over cooked).
Besides inadequate consumption what other ingested beverage can cause folic acid deficiency?
Alcohol- The primary metaboite for alcohol degrades folate in the colon. Folate acid deficiency is a common sign of alcoholism. Alcohol also inhibts absorption of folate.
What type of things cause malabsoprtion of folate?
Celiac’s disease and Alcohol.
How will drugs cause folic acid deficiencies?
Folic acid is a sticky molecule and drugs stick to it and render folic acid inert. (phenytoin, sulfasalzine, methotrexate, septra)
What type of people have an increased requirement for folic acid?
1) pregnancy 2) infancy 3) malignancy 4) exfoliative skin diseases.
What will lab findings be like for folic acid deficiencies?
hematologic and routine serum chemistry same as B12.
IF you have an anemia and suspect a folic acid deficiency what special chemistry tests should you do?
Serum folate- which would be decreased. Serum homocysteine- which should be increased.
What would a CBC look like for a patient that has anemia due to a chronic illness?
- 80 % of the time it will be Low HgB, HcT= anemia. Normal MCV= normocytic. Normal MCH, MCHC= normochromic. 2. 20% of the time due to blocked release of iron by macrophages during transfer and will cause decreased HgB, HCT= anemia. Decreased MCV= microcytic. and decreased MCH, MCHC= hypochromic.
Name 6 chronic diseases that commonly produce anemia?
1) renal 2) liver 3) rheumatologic (inflammatory) 4) infectious 5) malignant 6) endocrinologic.
What is pancytopenia?
a condition of hypoplastic bone marrow that suppresses erythropoietic activity or replaces active healthy marrow with fibrotic or malignant tissue and occurs to the entire myeloid hematopoietic activity. The marrow activity can be totally suppressed in some cases and this is called aplastic anemia.
What are 2 general causes of depletion (hemolytic)anemias?
- Extracorpuscular agent induced (aquired). 2. Intracorpuscular defect induced (inherited).
What is induced by a extracorpuscular agent?
Normal number and normal blood cells are produced but they are attacked: 1) immunohemolytic 2)traumatic 3) toxin 4) parastic.
What is induced by intracorpuscular defect ?
Bone marrow produces bad RBC that will be destroyed.
What are the 3 types of negative RBC produced due to intracorpuscular defects?
- hemoglobin abnormalities 2. RBC membrane abnormalities 3. RBC enzyme abnormalites.
What are two examples of hemoglobin abnormalities caused by intracorpuscular defect?
Thalasemias and Hemoglobin S disorders (Sickle Cell)
What is an example of a RBC membrane abnormality caused by intracorpuscular defect?
What is an example of a RBC enzyme abnormality caused by intracorpuscular defect?
What would the results be of a CBC for a patient with a hemolysis anemia?
Low HgB, HCT= anemia. Reticulocytosis (increase of immature RBC showing bone marrow is active and trying to make up for anemia).
What would the results be for a serum test on a patient with hemolysis anemia?
Since RBC are lysing you would have unconjugated hyperbilirubinemia and increased LDH (since RBC are full of LDH and heme- which is converted into unconjugated bilirubin once outside the RBC). In extreme cases the plasma can turn pink due to free hemoglobin.
What would the urine tests show with a hemolytic anemia?
Hemoglobinuria- presence of hemoglobin in urine not RBC. Hematuria- would not be seen with hemolytic anemias and this is the presence of RBC in urine.
What would be seen on x-ray of a hemolytic anemic patient?
Erythroid hyperplasia causing thinning of the bone.
What is immunohemolytic anemias that cause extracorpuscular agent induced hemolytic anemais?
Intravascular or intrasplenic hemolysis of RBC due to either isoantibodies or autoantibodies. (complement system breakdown of RBC in blood vessels)
Name a disease that is immunohemolytic anemia?
Hemolytic disease of the newborn (HDN).
How will traumatic events cause extracorpuscular induced anemias?
Physical trauma to RBC causes hemolysis.
What are events that can cause traumatic hemolytic anemias?
May occur in malignant hypertension, surgical replaced heart valves, reptetive external blows to the body.
Name 3 things that can cause toxic hemolytic anemias?
Chemicals, burns, snake venoms.
How will parasites cause hemolytic anemais?
The plasmodium parasite (malaria) causes hemolysis during its lifestyle.
How can you diagnose malaria?
During patients high fever take a blood sample and do a smear and look for parasites.
What type of anemia will thalassemias be?***
What are Thalessemias?
Thalassemias are a heterogenous group of inheritied disorders involving a defect in the genes that control alpha and beta globin chain synthesis
What are the 3 things that can lead to thalassemias?
Hypoproilferative anemia, hemolytic anemia, and abnormal hemoglobin synthesis.
What are the 2 types of thalassemias and how can you tell them apart on a CBC?
Alpha- no increased RBC. Beta- increased RBC starting with the minor beta thalassemias.
What type of people are more likely to have a thalassemia Alpha and Beta?
Alpha- SE Asians, Chinese, and blacks. Beta- mediterraneans, Chinese, other Asians and blacks.
Genetically what causes Alpha and Beta thalassemias?
Alpha- you inherit one, two, three, or four gene deletions that reduce the synthesis of alpha chains. Beta- point mutations of genes may produce a homozygous or heterozygous reduction of beta chains.
With a minor (1-2 gene) deletion, what clinical changes would be seen?
Minor hemtologic changes, no clinical signs and symptoms, and normal life expectancy
With a 3 gene deletion, what clinical changes would be seen?
Results in the formation of four beta chain tetramers called Hemoglobin H. Affected RBCs poorly deliver oxygen, are unstable and subject to oxidative denaturation (infection and oxidative drugs). Patients reveal pallor and splenomegaly, and may require transfusions during hemolytic exacerbations d/t episodes of oxidative stress
With a 4 gene deletion, what clinical changes would be seen?
Results in stillborn fetus d/t hydrops fetalis
What will the Hemoglobin electrophosesis look like for Beta thalasemias?
Decreased HbA1 and increased HbA2 and HbF.
What will cause a minor vs more serious alpha thalassemia?
Minor is d/t one- two gene deletions, three is more serious. Four gene deletions will result in a stillborn fetus.
With Beta Thalessemias, what form is more serious the homozygous forms or the heterozygous forms?
What do the heterozygous forms (minima and minor) cause (at most)?
An insignificant mild microcytic and hypochromic anemia
What does the homozygous form (intermedia and major) of beta thalassemias cause?
Homozygous- excess alpha chains are unstable and percipitate leading to damaged RBC membranes which leads to intramedullary and intravascular hemolysis with increased hemolysis and ineffective EPO the bone marrow becomes hyperplastic and expands leading to bony deformities.
What are the different manifestations of beta thalassemia?
Minima, minor, intermedia and major.
Which beta thalassemias will be anemic?
Minor, intermedia and major with Increased RBC.
What do beta thalassemia intermedia cause?
Causes a chronic hemolytic anemia, may require transfusions during times of stress (can subsequently develop iron overload) and have hepatosplenomegaly and bony deformities
What do beta thalassemia major cause?
Major patients are normal up to approximately six months when severe anemia develops which require transfusions; abnormalities ensue: growth failure, bony deformities (facial structure, pathologic fracture), hepatoplenomegaly and jaundice.
Will transfusions help with beta thalessemia major?
Yes but eventually lead to iron overload (similar to hemochromatosis) with associated heart failure, cirrhosis and endocrinopathies
What will a CBC look like for Alpha thalassemias?
a decreased MCV and MCH with Target cells. (norm-slightly decreased MCV & MCH for silent carriers and Decreased MCV & MCH with NRBC for Barts Hydrops Fetalis)
What will a CBC look like for beta thalassemias?
Decreased MCV and MCH but increased RBC’s with target cells and stippling and nucleated RBCs
What are the four types of alpha thalassemias?
Silent carrier state, alpha thalassemia minor (trait), Hemoglobin H disease, Barts hydrops fetalis
What are the 4 types of beta thalassemias?
Beta thalassemia minima, Beta thalassemia minor, Beta thalassemia intermedia, Beta thalassemia major (Cooley’s anemia)
Which of the thalassemias will cause changes in life expectancy?
Only Beta Thalassemia Major (20-30 years) and Barts Hydrops Fetalis (Fatal), Hemoglobin H disease and Beta Thalassemia intermedia are normal with clinical problems
Which thalassemias have a normal hemoglobin electrophoresis?
Silent carrier state, alpha thalassemia minor and beta thalassemia minima
What hemoglobin electrophoresis changes are seen with Hemoglobin H disease?
Variable HbA1 and HbA2 and 10-40% of Hb H
What hemoglobin electrophoresis changes are seen with Barts Hydrops Fetalis?
Hb Barts and Hb Portland
What hemoglobin electrophoresis changes are seen with beta thalassemia minor?
Variable HbA1 and HbA2 and normal to slight increased HbF
What hemoglobin electrophoresis changes are seen with beta thalassemia intermedia?
Decreased HbA1 and variable HbA2 normal to slight increased HbF
What hemoglobin electrophoresis changes are seen with beta thalassemia major?
Decreased HbA1 and variable HbA2 increased HbF
How can you tell an Iron deficiency from a thalassemia from a CBC?
Both will have decreased MCV but Iron anemias will rearely lower the MCV below 70 and Thalassemias will often lower the MCV below 70.
Is hemoglobin S abnormalities a thalassemia?
Genetically what causes hemoglobin S abnormalities?
Point mutations that substitute valine for glutamine in the 6th position of the beta chain.
What will hemoglobin S abnormalities do to hemoglobin?
HbS forms polymers that damage the RBC membrane and cause sickling.
Sickling of RBC is primarily influenced by what?
The amount of HbS present and hypoxemia.
Early damage to RBC from HbS can do what?
it can be reversible, but multiple episodes causes irreversible sickling.
What are the 2 types of hemoglobin S abnormalities?
Sickle cell trait. Sickle Cell anemia.
What is the genetic difference between Sickle cell trait and sickle cell anemia?
Sickle cell trait- heterozygous. Sickle cell anemia- Homozygous.
Who will be more likely to get sickle cell trait and by how much?
American blacks and 8% will have it.
What will sickle cell trait be like?
usually no hemolytic episodes or complications, but in rare instances sickling crisis can occur when patient is involved in vigorous exercies and exposed to an extremely hypoxic environment. They may have renal tubular function abnormalities resulting in dilute urine and hematuria (unexplained).
What tests can be done on someone suspected of sickle cell trait?
(+) dithinoite solubility test for HgB S, and HgB electrophoresis will show some HgB S at about 35-45%.
What % of American blacks will have sickle cell anemia?
What will sickle cell anemia be like?
Failure to thrive becomes apparent within 6 months after birth. Vasoclusive phenomena results in multiple system involvment; skeleton, viscera, skin and eyes.
What are the lab findings like for sickle cell anemia?
Marked anemia, circulating sickle cells, circulating nucleated RBC’s (immature), reactive leukocytosis (due to tissue necrosis), reactive thrombocytosis, 80% HgB S from electrophoresis.
What are 3 things that can happen to sickled RBC?
Lysis, clumping and clogging small blood vessels, accumulate in spleen.
What will a CBC for a sickle cell anemia patient look like?
Really low RBC, Low HgB and HcT. Low leukocytes and will show target cells and sickle cells.
What do target cells signify?
What are the 3 types of intracorpuscular defect induced hemolytic anemias?
1) HMG abnormalities ie:(Thalassemias and sickle cell) 2) Abnormal cell membrane ie: hereditary spherocytosis 3) Abnormal enzyme ie: Glucose-6-phosphate dehydrogenase (G6PD) deficiency
What will Hereditary spherocytosis cause?
RBC membrane abnormality where surface area is decreased reulting in loss of biconcavity therefore losing pliability. It is rare
What is the only condition to cause hyperchromic and microcytic indices?
What will a glucose-6-phosphate dehyrogenase (G6PD) deficiency cause?
A lack in NADPH which is needed to resist oxidative stress and hemoglobin becomes unstable causing lysis.
What can cause the oxidative stress?
Acute infections, foods (like fava bean = favism), drugs, etc.
What is another name for G6PD deficiency?
favism and this comes from fava beans which have a chemical that can cause G6PD deficiency.