Blood cell disorders Flashcards
In relation to myelofibrosis, which of the following statements is false?
A Supresses extramedullary hematopoiesis
B Stimulates erythropoetin production
C Causes leukoerythroblastic anaemia
D Casues an increase in megakaryocytes
A
Explanation
Myelofibrotic obliteration of the marrow space leads to extensive extramedullary haematopoeisis, principally in the spleen. There is a tri-linear haematopoietic proliferation, often with a predominance of megakaryocytes. Laboratory findings include a severe normochromic normocytic anaemia accompanied by leukoerythroblastosis. The serum erythropoietin level in idiopathic myelofibrosis appears to be appropriately elevated to the degree of anaemia in most patients, but this observation may be misleading because the observed increase in circulating erythropoietin is not sufficient to correct the anaemia- a situation common to anaemia of chronic disease. Thus with symptomatic anaemia and with serum erythropoietin levels less than 200mU/ml, a trial of recombinant human erythropoietin is appropriate
With regard to thrombocytopenia, which of the following statements is false?
A Occurs with hyposplenism
B Is associated with megaloblastic anaemia
C Causes spontaneous bleeding at levels of less than 20,000/uL
D Occurs commonly in HIV patients
A
Explanation
Thrombocytopaenia (platelet counts of less than 100,000uL may be associated with spontaneous bleeding at platelet counts < 20,000/uL. Counts of between 20,000-50,000/uL are associated (can aggravate) with post traumatic bleeding. Bleeding resulting from thrombocytopenia is associated with a normal PT and PTT
Thrombocytopenia is associated with megaloblastic anaemia and occurs in HIV cases, it is the most common haematological manifestation. Hypersplenism causes a thrombocytopaenia through platelet sequestration.
Macrocytic anaemia is associated with all the following except?
A Hypothyroidism
B Pregnancy
C Neoplasm
D Epstein–Barr virus (EBV)
D
Explanation
One of the most common causes of macrocytic anaemias are the megaloblastic anaemia, in which cells are larger because they cannot produce DNA quickly enough to divide at the right time as they grow, thus growing too large before division. Megaloblastic anaemia is caused by a vitamin B12 deficiency, folic acid deficiency, or due to unresponsiveness to vitamin B12, or folic acid therapy. Pregnancy and disseminated cancer all have an increased requirement for B12.
Hypothyroidism- Macrocytosis is found in up to 55% patients with hypothyroidism and may result from the insufficiency of the thyroid hormones themselves without nutritive deficit.
A nice explanation
Macrocytic anemia
First, let’s just review macrocytic anemias quickly. There are two kinds of macrocytic anemias: megaloblastic ones and non-megaloblastic ones.
The megaloblastic anemias have a problem with DNA synthesis. Something (usually B12 and/or folate deficiency) is inhibiting DNA synthesis, but RNA synthesis is proceeds as usual. So, you get big cells (the cell cycle, and hence cell division, takes longer due to the impaired DNA synthesis – so the cells grow big before dividing). There is also nuclear:cytoplasmic asynchrony, meaning that the nucleus is immature compared to the maturity of the cytoplasm (because the synthesis of DNA in the nucleus is impaired, whereas the RNA in the cytoplasm is just fine). These cells are called megaloblasts.
The non-megaloblastic anemias don’t have a problem with DNA synthesis. Uncomplicated anemia in liver disease (e.g., plain old macrocytic anemia without superimposed iron-deficiency anemia or anemia of blood loss) can be macrocytic, as can anemia in alcoholism. The mechanism in these types of anemias is different. In liver disease, it has to do with insertion of cholesterol into the red cell membrane, which expands the membrane and makes the cell bigger. Ok, so far so good.
Here are the corrections to the errors
1) Drugs that impair DNA synthesis (including the ones you mention: 5-FU, AZT and hydroxyurea) do, in fact, cause megaloblastic anemia. Their mechanism involves inhibition of DNA synthesis, so just as in B12/folate deficiency, you would get a megaloblastosis!
2) You do NOT get a macrocytic anemia from reticulocytosis. Let’s just get that out in the open and cleared up right now. It’s a common misconception that if you have a patient with a lot of reticulocytes, that can make the MCV bump up above the normal range. But it’s not true! You just need to do the math to see that it can’t happen.
Normal red cells are between 80 and 100 fL. Reticulocytes are bigger than normal red cells, but not that much bigger. You can see them in the supravital stain above; they’re the ones with the blue dots/strings. They are somewhere between 103 and 120 fL. So let’s say you have a normal MCV (around 90), and let’s say retics are an average of 115 fL. To get the MCV up into the macrocytic range by just adding reticulocytes, you’d have to have at least 40% reticulocytes (60% at 90, and 40% at 115). The retic count never gets that high in humans! It can get as high as 15%, or even 20%, but it just doesn’t get up to 40%. It does in animals, but not in humans. So while it sounds good in theory (retics are bigger, add retics and the MCV will go up) it just doesn’t work out in practice.
Source: https://www.pathologystudent.com/does-reticulocytosis-cause-a-macrocytic-anemia/
Regarding disseminated intravascular coagulation which of the following is INCORRECT?
A Platelets levels usually remain unchanged
B Gram-negative sepsis is a cause of DIC
C The only definitive treatment is removal of the underlying cause
D Activated partial thromboplastin time (APTT) is increased
E Decreased fibrinogen levels
A
Explanation
In DIC, fibrinogen levels are decreased as they are converted into fibrin. APTT is markedly increased. Thrombocytopaenia occurs. Treatment of the underlying cause is the most important management of patients with DIC. Additional management includes protein C therapy and factor VIIa therapy There are multiple causes of DIC including hepatic failure, obstetric causes (amniotic fluid embolism, eclampsia, foetal death in utero), trauma, malignancy, immunological, sepsis (gram neg and viral haemorrhagic fever). DIC is never a primary disease
Which is the correct sequence of first to last laboratory abnormality seen with disseminated intravascular coagulation (DIC)?
A Elevated PT, hypofibrinogenemia, thrombocytopenia
B Thrombocytopenia, hypofibrinogenemia, elevated PT
C Thrombocytopenia, elevated PT, hypofibrinogenemia
D Hypofibrinogenemia, elevated PT, thrombocytopenia
E Elevated prothrombin time (PT), thrombocytopenia, hypofibrinogenemia
C
Explanation
Thrombocytopenia (low platelet count): This usually occurs early as the widespread activation of coagulation consumes platelets.
Prolonged PT and APTT (prothrombin time and activated partial thromboplastin time): These reflect the consumption of clotting factors as they are used up in the ongoing coagulation process.
Decreased fibrinogen levels: Fibrinogen is consumed in the formation of fibrin clots, leading to a decrease in circulating fibrinogen.
Elevated D-dimer: D-dimer is a degradation product of fibrin, and its elevation indicates increased fibrinolysis (breakdown of blood clots), a compensatory mechanism that occurs as the body tries to control the excessive clotting.
Elevated Fibrin Degradation Products (FDPs): Similar to D-dimer, elevated FDPs further reflect the increased fibrinolysis.
Important Considerations:
Overlap: These abnormalities often overlap and don’t always appear in this precise order. Some might be present before others, or some might be more pronounced than others.
Other markers: Other laboratory findings may be present, such as decreased hematocrit (due to bleeding and consumption of red cells), and increased levels of certain clotting factors (initially). This depends on the balance of clotting and fibrinolysis.
Subtleties: In some cases of DIC, the abnormalities may be subtle, making diagnosis challenging.
General-extra
In DIC, fibrinogen levels are decreased as they are converted into fibrin. Thrombocytopaenia occurs. D-dimer levels are elevated. APTT and PT levels are increased. Decreased factors V and VIII. Treatment of the underlying cause is the most important management of patients with DIC. Additional management includes protein C therapy and factor VIIa therapy There are multiple causes of DIC including hepatic failure, obstetric causes (amniotic fluid embolism, eclampsia, foetal death in utero), trauma, malignancy, immunological, sepsis (gram neg and viral haemorrhagic fever).
Extra: The laboratory abnormalities reported in DIC listed in the decreasing order of frequency are thrombocytopenia, elevated fibrin degradation products (FDPs), prolonged PT, aPTT and a low fibrinogen. In early DIC, the platelet count and fibrinogen levels may remain within the normal range, albeit reduced from baseline levels.
Source: DIC-www.ncbi.nlm.nih.gov/pmc/articles/PMC4260307/
