In addition to the three basic rune types; blood, frost and unholy, there is a fourth unique type of rune known as a death rune.
Death runes are special in that they temporarily replace one of your normal runes and allow you to utilize it to power your abilities, as if it was a rune of any needed type. Death runes allow a great deal of flexibility in your combat rotations by allowing you to swap weaker attacks for stronger ones or giving you more chances to utilize your reactive abilities.
Death runes are generated in two unique ways; the first is through talents or unique item bonuses that cause any rune consumed by a specific ability to become a death rune. This change in rune type is temporary, lasting until you either consume the rune, upon which it will return to its default type, or it will revert back to its default state after spending long enough out of combat.
Since death runes generated in this fashion start off on cool down they are generally only of great use for creating higher damage output rotations and burst damage since they allow you to utilize your strongest attacks more times in quick succession during a rotation.
The second way you can generate death runes is by the ability Blood Tap which instantly converts one of your blood runes into a death rune at the cost of a little health; it will also refresh the rune cool down, making it available for immediate use.
Unlike other death runes, the rune generated from Blood Tap will remain a death rune for 20 seconds before reverting to its normal state, allowing it to be utilized multiple times. Also, since the rune is immediately activated, Blood Tap provides you with the capability to quickly utilize a reactive ability without prior planning, making it a vital tool for effective PvP and for emergency survival.
There is a knack to utilizing death runes properly however, since if you do not time your abilities carefully timed you can find that you mess up your rotations. An example of this would be if you were anticipating a death rune, a frost rune and two unholy runes to activate and planned to utilize two strikes that consume a frost and an unholy rune.
If your death rune and frost rune activated first and you were just spamming your attack then you would instantly use up the runes and be left with two unholy runes that would be unable to be used for a second attack. By understanding how your abilities consume runes you can avoid this.
When any ability is used, it will always consume ordinary runes before death runes; if it cannot find sufficient runes then it will check for any death runes and consume one of them instead. So if in the above situation, you waited for all of the runes to come off cool down; the first strike would consume one frost and one unholy rune while the second would consume the remaining unholy rune and find no frost rune, so will use the death rune instead.
By keeping an eye on the order in which your runes activate, you can ensure that you utilize them in the most effective way possible.